%0 journal article %@ 0003-2700 %A Eselem Bungo, P.S.,Lützow, K.,Lettau, O.,Schulz, M.,Neffe, A.T.,Pasch, H. %D 2024 %J Analytical Chemistry %N 11 %P 4716-4725 %R doi:10.1021/acs.analchem.4c00336 %T Stereochemical heterogeneity analysis of polylactides by multidimensional liquid chromatography %U https://doi.org/10.1021/acs.analchem.4c00336 11 %X A new and robust high-performance liquid chromatography (HPLC) method that separates poly(lactic acid) (PLA) according to its stereochemical composition is presented. Using this method, poly(l-lactide) incorporating trace amounts of meso-lactide resulting from the racemization is separated from the pristine polymer. To prove this aspect in more detail, a representative poly(l-lactic acid) standard, assumed to be highly homogeneous, was separated using this method. The result showed that this was not the case as a fraction incorporating meso-lactide due to racemization occurring during the synthesis is separated. Employing two-dimensional liquid chromatography (2D-LC), the molar mass differences of the separated species were investigated, and fractions with similar molecular sizes were detected, confirming that the LC separation is solely based on stereochemical heterogeneity. The sample was further fractionated by preparative HPLC, followed by an in-depth analysis of the fractions using homonuclear decoupling in proton nuclear magnetic resonance (1H NMR). Convincing results that unveiled significant differences in the stereochemistry of the isolated PLA fractions were obtained. Subsequent analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) also confirmed oligomer series with different end group structures, indicating that the applied HPLC method is very sensitive to minor variations in stereochemistry and end groups. This integrated approach offers detailed insight into the structural characteristics of PLA polymers, contributing to a better understanding of their composition and potential applications. %0 journal article %@ 1422-0067 %A Balk, M.,Sofia, P.,Neffe, A.T.,Tirelli, N. %D 2023 %J International Journal of Molecular Sciences %N 14 %P 11668 %R doi:10.3390/ijms241411668 %T Lignin, the lignification process, and advanced, lignin-based materials %U https://doi.org/10.3390/ijms241411668 14 %X At a time when environmental considerations are increasingly pushing for the application of circular economy concepts in materials science, lignin stands out as an under-used but promising and environmentally benign building block. This review focuses (A) on understanding what we mean with lignin, i.e., where it can be found and how it is produced in plants, devoting particular attention to the identity of lignols (including ferulates that are instrumental for integrating lignin with cell wall polysaccharides) and to the details of their coupling reactions and (B) on providing an overview how lignin can actually be employed as a component of materials in healthcare and energy applications, finally paying specific attention to the use of lignin in the development of organic shape-memory materials. %0 journal article %@ 1438-7492 %A Folikumah, M.Y.,Behl, M.,Lendlein, A.,Neffe, A.T. %D 2023 %J Macromolecular Materials and Engineering %N 11 %P 2300146 %R doi:10.1002/mame.202300146 %T A 4-Arm PEG-Thiodepsipeptide Precursor Enables Gelatinase-promoted Hydrogel Formation %U https://doi.org/10.1002/mame.202300146 11 %X In situ hydrogelation of injectable precursors upon biological stimulus is relevant to generate hydrogels under mild conditions and, potentially, at a biological side of interest. Here, it is shown that hydrolytic enzymes can be used to initiate the formation of covalent hydrogel networks, realizing a cleavage-leading-to-gelation strategy. For this purpose, a two-component system is used, consisting of a 4-arm polyethylene glycol-thiodepsipeptide conjugate, PEG4TDPo containing the matrix metalloproteinases MMP-2- and MMP-9-cleavable Ac-Pro-Leu-Gly#SLeu-Leu-Gly- thiodepsipeptide sequence releasing a thiol upon hydrolysis, and a maleimide functionalized 4-armed PEG (PEG4MAL). PEG4TDPo is synthesized in a PEG-functionalization protocol involving convergent and divergent synthetic steps without the need for rigorous purification procedures. In a fluorometric assay, it is shown that the construct is in fact cleaved by both investigated MMPs. PEG4TDPo in the presence of 10 wt.% PEG4MAL formed hydrogels upon addition of MMP-2 or -9 with average gelation times of 28 and 40 min, respectively, as is investigated by rheology. The much faster gelation times compared to the enzyme-free system showed the specific input of the enzymatic reactions. The MMP-assisted activation and crosslinking strategy can potentially become useful by targeting tissues showing an increased expression of MMPs, such as cancers, or to detect MMPs. %0 journal article %@ 2046-2069 %A Kirchhecker, S.,Nguyen, N.,Reichert, S.,Lützow, K.,Eselem Bungu, P.S.,van Wangelin, A.J.,Sandl, S.,Neffe, A.T. %D 2023 %J RSC Advances %N %P 17102-17113 %R doi:10.1039/d3ra03112h %T Iron(II) Carboxylates and Simple Carboxamides: An Inexpensive and Modular Catalyst System for the Synthesis of PLLA and PLLA-PCL Block Copolymers; %U https://doi.org/10.1039/d3ra03112h %X The combination of inexpensive Fe(II) acetate with low molecular weight aliphatic carboxamides in situ generates an effective catalyst system for the ring opening polymerisation of lactones. PLLAs were produced in melt conditions with molar masses of up to 15 kg mol−1, narrow dispersity (Đ = 1.03), and without racemisation. The catalytic system was investigated in detail with regard to Fe(II) source, and steric and electronic effects of the amide's substituents. Furthermore, the synthesis of PLLA-PCL block copolymers of very low randomness was achieved. This commercially available, inexpensive, modular, and user-friendly catalyst mixture may be suitable for polymers with biomedical applications. %0 journal article %@ 2073-4360 %A Farhan, M.,Hartstein, D.S.,Pieper, Y.,Behl, M.,Lendlein, A.,Neffe, A.T. %D 2023 %J Polymers %N 9 %P 2233 %R doi:10.3390/polym15092233 %T Bio-inspired magnetically controlled reversibly actuating multimaterial fibers %U https://doi.org/10.3390/polym15092233 9 %X Movements in plants, such as the coiling of tendrils in climbing plants, have been studied as inspiration for coiling actuators in robotics. A promising approach to mimic this behavior is the use of multimaterial systems that show different elastic moduli. Here, we report on the development of magnetically controllable/triggerable multimaterial fibers (MMFs) as artificial tendrils, which can reversibly coil and uncoil on stimulation from an alternating magnetic field. These MMFs are based on deformed shape-memory fibers with poly[ethylene-co-(vinyl acetate)] (PEVA) as their core and a silicone-based soft elastomeric magnetic nanocomposite shell. The core fiber provides a temperature-dependent expansion/contraction that propagates the coiling of the MMF, while the shell enables inductive heating to actuate the movements in these MMFs. Composites with mNP weight content ≥ 15 wt% were required to achieve heating suitable to initiate movement. The MMFs coil upon application of the magnetic field, in which a degree of coiling N = 0.8 ± 0.2 was achieved. Cooling upon switching OFF the magnetic field reversed some of the coiling, giving a reversible change in coiling ∆n = 2 ± 0.5. These MMFs allow magnetically controlled remote and reversible actuation in artificial (soft) plant-like tendrils, and are envisioned as fiber actuators in future robotics applications. %0 editorial %@ 1422-0067 %A Neffe, A.T. %D 2023 %J International Journal of Molecular Sciences %N 7 %P 6057 %R doi:10.3390/ijms24076057 %T Cell-Material Interactions 2022 %U https://doi.org/10.3390/ijms24076057 7 %X %0 journal article %@ 1616-301X %A Tung, W.T.,Maring, J.A.,Xu, X.,Liu, Y.,Becker, M.,Somesh, D.B.,Klose, K.,Wang, W.,Sun, X.,Ullah, I.,Kratz, K.,Neffe, A.T.,Stamm, C.,Ma, N.,Lendlein, A. %D 2022 %J Advanced Functional Materials %N 31 %P 2110179 %R doi:10.1002/adfm.202110179 %T In Vivo Performance of a Cell and Factor Free Multifunctional Fiber Mesh Modulating Postinfarct Myocardial Remodeling %U https://doi.org/10.1002/adfm.202110179 31 %X Guidance of postinfarct myocardial remodeling processes by an epicardial patch system may alleviate the consequences of ischemic heart disease. As macrophages are highly relevant in balancing immune response and regenerative processes their suitable instruction would ensure therapeutic success. A polymeric mesh capable of attracting and instructing monocytes by purely physical cues and accelerating implant degradation at the cell/implant interface is designed. In a murine model for myocardial infarction the meshes are compared to those either coated with extracellular matrix or loaded with induced cardiomyocyte progenitor cells. All implants promote macrophage infiltration and polarization in the epicardium, which is verified by in vitro experiments. 6 weeks post-MI, especially the implantation of the mesh attenuates left ventricular adverse remodeling processes as shown by reduced infarct size (14.7% vs 28–32%) and increased wall thickness (854 µm vs 400–600 µm), enhanced angiogenesis/arteriogenesis (more than 50% increase compared to controls and other groups), and improved heart function (ejection fraction = 36.8% compared to 12.7–31.3%). Upscaling as well as process controls is comprehensively considered in the presented mesh fabrication scheme to warrant further progression from bench to bedside. %0 conference lecture (invited) %@ %A Neffe, A. %D 2022 %J FGW Partnering Workshop 2022 : Biofunktionalisierung von Materialien in Medizin und Gesundheit %N %P %T Ansätze und Fallstricke in der transferorientierten Forschung aus Sicht des Wissenschaftlers %U %X %0 journal article %@ 2079-4991 %A Neffe, A.,Izraylit, V.,Hommes-Schattmann, P.,Lendlein, A. %D 2021 %J Nanomaterials %N 6 %P 1472 %R doi:10.3390/nano11061472 %T Soft, Formstable (Co)Polyester Blend Elastomers %U https://doi.org/10.3390/nano11061472 6 %X High crystallization rate and thermomechanical stability make polylactide stereocomplexes effective nanosized physical netpoints. Here, we address the need for soft, form-stable degradable elastomers for medical applications by designing such blends from (co)polyesters, whose mechanical properties are ruled by their nanodimensional architecture and which are applied as single components in implants. By careful controlling of the copolymer composition and sequence structure of poly[(L-lactide)-co-(ε-caprolactone)], it is possible to prepare hyperelastic polymer blends formed through stereocomplexation by adding poly(D-lactide) (PDLA). Low glass transition temperature Tg ≤ 0 °C of the mixed amorphous phase contributes to the low Young’s modulus E. The formation of stereocomplexes is shown in DSC by melting transitions Tm > 190 °C and in WAXS by distinct scattering maxima at 2θ = 12° and 21°. Tensile testing demonstrated that the blends are soft (E = 12–80 MPa) and show an excellent hyperelastic recovery Rrec = 66–85% while having high elongation at break εb up to >1000%. These properties of the blends are attained only when the copolymer has 56–62 wt% lactide content, a weight average molar mass >140 kg·mol−1, and number average lactide sequence length ≥4.8, while the blend is formed with a content of 5–10 wt% of PDLA. The devised strategy to identify a suitable copolymer for stereocomplexation and blend formation is transferable to further polymer systems and will support the development of thermoplastic elastomers suitable for medical applications. %0 journal article %@ 1386-0291 %A Brunacci, N.,Wischke, C.,Naolou, T.,Patzelt, A.,Lademann, J.,Neffe, A.,Lendlein, A. %D 2021 %J Clinical Hemorheology and Microcirculation %N 2 %P 201-219 %R doi:10.3233/CH-200977 %T Formulation of drug-loaded oligodepsipeptide particles with submicron size %U https://doi.org/10.3233/CH-200977 2 %X The size of particulate carriers is key to their transport and distribution in biological systems, and needs to be tailored in the higher submicron range to enable follicular uptake for dermal treatment. Oligodepsipeptides are promising nanoparticulate carrier systems as they can be designed to exhibit enhanced interaction with drug molecules. Here, a fabrication scheme for drug-loaded submicron particles from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diol (OBMD) is presented based on an emulsion solvent evaporation method with cosolvent, surfactant, and polymer concentration as variable process parameters. The particle size (300–950 nm) increased with lower surfactant concentration and higher oligomer concentration. The addition of acetone increased the particle size at low surfactant concentration. Particle size remained stable upon the encapsulation of models compounds dexamethasone (DXM) and Nile red (NR), having different physicochemical properties. DXM was released faster compared to NR due to its higher water solubility. Overall, the results indicated that both drug-loading and size control of OBMD submicron particles can be achieved. When applied on porcine ear skin samples, the NR-loaded particles have been shown to allow NR penetration into the hair follicle and the depth reached with the 300 nm particles was comparable to the one reached with the cream formulation. A potential benefit of the particles compared to a cream is their sustained release profile. %0 journal article %@ 2059-8521 %A Neffe, A.,Zhang, Q.,Hommes-Schattmann, P.,Lendlein, A. %D 2021 %J MRS Advances %N 33 %P 786-789 %R doi:10.1557/s43580-021-00058-5 %T Ethylene oxide sterilization of electrospun poly(l-lactide)/poly(d-lactide) core/shell nanofibers %U https://doi.org/10.1557/s43580-021-00058-5 33 %X The application of polymers in medicine requires sterilization while retaining material structure and properties. This demands detailed analysis, which we show exemplarily for the sterilization of PLLA/PDLA core–shell nanofibers with ethylene oxide (EtO). The electrospun patch was exposed to EtO gas (6 vol% in CO2, 1.7 bar) for 3 h at 45 °C and 75% rel. humidity, followed by degassing under pressure/vacuum cycles for 12 h. GC–MS analysis showed that no residual EtO was retained. Fiber diameters (~ 520 ± 130 nm) of the patches remained constant as observed by electron microscopy. Young’s modulus slightly increased and the elongation at break slightly decreased, determined at 37 °C. No changes were detected in 1H-NMR spectra, in molar mass distribution (GPC) or in crystallinity measured for annealed samples with comparable thermal history (Wide Angle X-Ray Scattering). Altogether, EtO emerged as suitable sterilization method for polylactide nanofibers with core–shell morphology. %0 journal article %@ 1422-0067 %A Neffe, A.,Löwenberg, C.,Julich-Gruner, K.,Behl, M.,Lendlein, A. %D 2021 %J International Journal of Molecular Sciences %N 11 %P 5892 %R doi:10.3390/ijms22115892 %T Thermally-Induced Shape-Memory Behavior of Degradable Gelatin-Based Networks %U https://doi.org/10.3390/ijms22115892 11 %X Shape-memory hydrogels (SMH) are multifunctional, actively-moving polymers of interest in biomedicine. In loosely crosslinked polymer networks, gelatin chains may form triple helices, which can act as temporary net points in SMH, depending on the presence of salts. Here, we show programming and initiation of the shape-memory effect of such networks based on a thermomechanical process compatible with the physiological environment. The SMH were synthesized by reaction of glycidylmethacrylated gelatin with oligo(ethylene glycol) (OEG) α,ω-dithiols of varying crosslinker length and amount. Triple helicalization of gelatin chains is shown directly by wide-angle X-ray scattering and indirectly via the mechanical behavior at different temperatures. The ability to form triple helices increased with the molar mass of the crosslinker. Hydrogels had storage moduli of 0.27–23 kPa and Young’s moduli of 215–360 kPa at 4 °C. The hydrogels were hydrolytically degradable, with full degradation to water-soluble products within one week at 37 °C and pH = 7.4. A thermally-induced shape-memory effect is demonstrated in bending as well as in compression tests, in which shape recovery with excellent shape-recovery rates Rr close to 100% were observed. In the future, the material presented here could be applied, e.g., as self-anchoring devices mechanically resembling the extracellular matrix. %0 conference lecture %@ %A Neffe, A.,Zhang, Q.,Hommes-Schattmann, P.,Wang, W.,Xu, X.,Ahmad, B.,Williams, G.,Lendlein, A. %D 2021 %J Virtual MRS Spring Meeting %N %P %T Multifunctionality by Core/Shell Design of PLLA/PDLA Nanofibres %U %X %0 journal article %@ 0014-3057 %A Neffe, A.,Garcia Cruz, D.,Roch, T.,Lendlein, A. %D 2021 %J European Polymer Journal %N %P 110148 %R doi:10.1016/j.eurpolymj.2020.110148 %T Microparticles from glycidylmethacrylated gelatin as cell carriers prepared in an aqueous two-phase system %U https://doi.org/10.1016/j.eurpolymj.2020.110148 %X Encapsulation by polymeric biomaterials can provide mechanical protection of cells and shielding from the immune system of the host when implanted as cell therapy. At the same time, free exchange of nutrients and metabolites including bioactive molecules guiding regenerative processes is facilitated. Here, glycidylmethacrylated gelatin (GMA-gelatin) is explored as matrix material for adherent (L929 mouse fibroblasts) or non-adherent (Ramos blue) cells by an integrated process of shaping and chemical crosslinking. Microparticle formation was driven by a water-in-water-emulsion technique, which allowed simultaneous irradiation with light of 365 nm in the presence of the photosensitizer irgacure 2959. Suitable photopolymerization conditions were determined in experiments with GMA-gelatin and cells. More than 85% of the cells survived this procedure, and an encapsulation efficiency of up to 75 ± 2% was reached. Diffusivity of molecules up to a molar mass of 150 kg·mol−1 in the matrix was shown by the release of co-encapsulated FITC-labelled dextran. L929 as well as Ramos blue cells proliferated in the microparticle matrix after encapsulation and released enzymes that could be detected in the cell culture medium in an active form. L929 showed the ability to escape the particles over time. Altogether, the presented cell encapsulation system based on a material that is stable to hydrolytic degradation for several weeks is generally suitable for cell based therapy or in vitro test systems. %0 journal article %@ 0884-2914 %A Neffe, A.,Zhang, Q.,Hommes-Schattmann, P.,Wang, W.,Xu, X.,Ahmad, B.,Williams, G.,Lendlein, A. %D 2021 %J Journal of Materials Research %N 14 %P 2995-3009 %R doi:10.1557/s43578-021-00260-z %T Functionalizable coaxial PLLA/PDLA nanofibers with stereocomplexes at the internal interface %U https://doi.org/10.1557/s43578-021-00260-z 14 %X Multifunctionality of electrospun polylactic acid (PLA) nonwovens was generated by the morphological design of nanofibers. Coaxial fibers with a lower number average molar mass Mn PLLA core and a higher Mn PDLA shell form PDLA–PLLA stereocrystals at the interface, induced by annealing. In tensile tests under physiological conditions, the core–shell fibers with higher crystallinity (22% compared to 11–14%) had lower Young’s moduli E (9 ± 1 MPa) and lower elongation at break εb (26 ± 3%) than PDLA alone (E = 31 ± 9 MPa, εb = 80 ± 5%), which can be attributed to simultaneous crystallization and relaxation effects. Gelatin incorporated in the PDLA phase was presented on the outer surface providing a biointerface putatively favorable for cell adherence. Gelatin incorporation did not influence the crystallization behavior but slightly lowered Tg (60 → 54 °C). Employing exclusively polymers established in the clinic, multifunctionality was generated by design. %0 journal article %@ 2059-8521 %A Neffe, A.,Löwenberg, C.,Lendlein, A. %D 2021 %J MRS Advances %N 33 %P 796-800 %R doi:10.1557/s43580-021-00136-8 %T Hydrogel networks by aliphatic dithiol Michael addition to glycidylmethacrylated gelatin %U https://doi.org/10.1557/s43580-021-00136-8 33 %X Functionalization of gelatin with glycidylmethacrylate (GMA-gelatin) enables network formation employing the double bond, so that the reaction is orthogonal to the inherent functional groups in the biomacromolecule. Here, network formation by crosslinking of GMA-gelatin with hexane 1,6-dithiol or nonane 1,9-dithiol to tailor properties and enable a shape-memory effect is shown by 1H NMR and FT-IR spectroscopy. Hydrogel swelling (460–1900 vol%) and mechanical properties (Young’s modulus E = 59–512 kPa, elongation at break εb = 44–127%) depended on the molecular composition of the networks and temperature. Increased crosslinker length, thiol:methacrylate molar ratio, and precursor concentrations led to denser networks. Change of properties with temperature suggested adoption of triple helices by gelatin chains, forming physical netpoints at lower temperatures (< 20 °C). However, the limited freedom of the gelatin chains to move allowed only a minimal extent of triple helices formation, as it became apparent from the related signal in wide-angle X-ray scattering and the thermal transition associated to triple helices in some networks by DSC. The presented strategy is likely transferable to other biomacromolecules, and the results suggest that too short crosslinkers may result in a significant amount of grafting rather than network formation. %0 journal article %@ 1386-0291 %A Krüger-Genge, A.,Tondera, C.,Hauser, S.,Braune, S.,Görs, J.,Roch, T.,Klopfleisch, R.,Neffe, A.,Lendlein, A.,Pietzsch, J.,Jung, F. %D 2021 %J Clinical Hemorheology and Microcirculation %N 3 %P 335-350 %R doi:10.3233/CH-201028 %T Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels %U https://doi.org/10.3233/CH-201028 3 %X Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the “Hen’s egg test on chorioallantoic membrane” (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants. %0 journal article %@ 2373-9878 %A Krüger-Genge, A.,Hauser, S.,Neffe, A.,Liu, Y.,Lendlein, A.,Pietzsch, J.,Jung, F. %D 2021 %J ACS Biomaterials Science & Engineering %N 2 %P 527-540 %R doi:10.1021/acsbiomaterials.0c01432 %T Response of Endothelial Cells to Gelatin-Based Hydrogels %U https://doi.org/10.1021/acsbiomaterials.0c01432 2 %X The establishment of confluent endothelial cell (EC) monolayers on implanted materials has been identified as a concept to avoid thrombus formation but is a continuous challenge in cardiovascular device engineering. Here, material properties of gelatin-based hydrogels obtained by reacting gelatin with varying amounts of lysine diisocyanate ethyl ester were correlated with the functional state of hydrogel contacting venous EC (HUVEC) and HUVEC’s ability to form a monolayer on these hydrogels. The density of adherent HUVEC on the softest hydrogel at 37 °C (G’ = 1.02 kPa, E = 1.1 ± 0.3 kPa) was significantly lower (125 mm–1) than on the stiffer hydrogels (920 mm–1; G’ = 2.515 and 5.02 kPa, E = 4.8 ± 0.8 and 10.3 ± 1.2 kPa). This was accompanied by increased matrix metalloprotease activity (9 pmol·min–2 compared to 0.6 pmol·min–2) and stress fiber formation, while cell-to-cell contacts were comparable. Likewise, release of eicosanoids (e.g., prostacyclin release of 1.7 vs 0.2 pg·mL–1·cell–1) and the pro-inflammatory cytokine MCP-1 (8 vs <1.5 pg·mL–1·cell–1) was higher on the softer than on the stiffer hydrogels. The expressions of pro-inflammatory markers COX-2, COX-1, and RAGE were slightly increased on all hydrogels on day 2 (up to 200% of the control), indicating a weak inflammation; however, the levels dropped to below the control from day 6. The study revealed that hydrogels with higher moduli approached the status of a functionally confluent HUVEC monolayer. The results indicate the promising potential especially of the discussed gelatin-based hydrogels with higher G’ as biomaterials for implants foreseen for the venous system. %0 journal article %@ 2159-6859 %A Lau, S.,Liu, Y.,Maier, A.,Braune, S.,Gossen, M.,Neffe, A.,Lendlein, A. %D 2021 %J MRS Communications %N 5 %P 559-567 %R doi:10.1557/s43579-021-00072-6 %T Establishment of an in vitro thrombogenicity test system with cyclic olefin copolymer substrate for endothelial layer formation %U https://doi.org/10.1557/s43579-021-00072-6 5 %X In vitro thrombogenicity test systems require co-cultivation of endothelial cells and platelets under blood flow-like conditions. Here, a commercially available perfusion system is explored using plasma-treated cyclic olefin copolymer (COC) as a substrate for the endothelial cell layer. COC was characterized prior to endothelialization and co-cultivation with platelets under static or flow conditions. COC exhibits a low roughness and a moderate hydrophilicity. Flow promoted endothelial cell growth and prevented platelet adherence. These findings show the suitability of COC as substrate and the importance of blood flow-like conditions for the assessment of the thrombogenic risk of drugs or cardiovascular implant materials. %0 journal article %@ 0014-3057 %A Izraylit, V.,Hommes-Schattmann, P.,Neffe, A.,Gould, O.,Lendlein, A. %D 2020 %J European Polymer Journal %N %P 109916 %R doi:10.1016/j.eurpolymj.2020.109916 %T Polyester urethane functionalizable through maleimide side-chains and cross-linkable by polylactide stereocomplexes %U https://doi.org/10.1016/j.eurpolymj.2020.109916 %X Sustainable multifunctional alternatives to fossil-derived materials, which can be functionalized and are degradable, can be envisioned by combining naturally derived starting materials with an established polymer design concept. Modularity and chemical flexibility of polyester urethanes (PEU) enable the combination of segments bearing functionalizable moieties and the tailoring of the mechanical and thermal properties. In this work, a PEU multiblock structure was synthesized from naturally derived L-lysine diisocyanate ethyl ester (LDI), poly(L-lactide) diol (PLLA) and N-(2,3-dihydroxypropyl)-maleimide (MID) in a one-step reaction. A maleimide side-chain (MID) provided a reactive site for the catalyst-free coupling of thiols shown for L-cysteine with a yield of 94%. Physical cross-links were generated by blending the PEU with poly(D-lactide) (PDLA), upon which the PLLA segments of the PEU and the PDLA formed stereocomplexes. Stereocomplexation occurred spontaneously during solution casting and was investigated with WAXS and DSC. Stereocomplex crystallites were observed in the blends, while isotactic PLA crystallization was not observed. The presented material platform with tailorable mechanical properties by blending is of specific interest for engineering biointerfaces of implants or carrier systems for bioactive molecules. %0 journal article %@ 1525-7797 %A Löwenberg, C.,Julich-Gruner, K.,Neffe, A.,Behl, M.,Lendlein, A. %D 2020 %J Biomacromolecules %N 6 %P 2024-2031 %R doi:10.1021/acs.biomac.9b01753 %T Salt-Induced Shape-Memory Effect in Gelatin-Based Hydrogels %U https://doi.org/10.1021/acs.biomac.9b01753 6 %X Hydrophilic biopolymers display a strong tendency for self-organization into stable secondary, tertiary, and quaternary structures in aqueous environments. These structures are sensitive to changes in external conditions, such as temperature, pH or ions/salts, which may lead to molecular and/or macroscopic transitions. Here, we report on biopolymer-based stimuli-sensitive switchable matrices showing a shape-memory function as an output being alternatively switched by two different input signals, such as environmental changes in salt concentration or temperature. This was realized by implementing a shape-memory function in hydrogels based on the coil-to-helix transition of protein chains in gelatin-based networks. The hydrogels exhibited mechanical properties similar to that of soft tissue (storage modulus G′ = 1–100 kPa) and high swelling capabilities (Q = 1000–3000 vol %). In these gelatin-based networks, the covalent netpoints defined the permanent shape while after deformation helicalization of the gelatin acted as reversible stimuli-sensitive switches providing additional crosslinks capable of fixing the deformed temporary shape. By using either chaotropic salts to suppress gelatin helicalization or kosmotropic salts to support conformational changes of gelatin toward a helical orientation, these additional crosslinks could be cleaved or formed. In bending experiments, the strain fixity (Rf) and strain recovery ratios (Rr) were determined. While Rf ranged from 65 to 95% and was depending on the network composition, Rr were independent of the hydrogel composition with values about 100%. In addition, Rf and Rr were independent of the type of chaotropic salt that was used in this study, showing equal Rf and Rr values for MgCl2, NaSCN, and Mg(SCN)2. %0 journal article %@ 0014-3057 %A Izraylit, V.,Hommes-Schattmann, P.,Neffe, A.,Gould, O.,Lendlein, A. %D 2020 %J European Polymer Journal %N %P 109908 %R doi:10.1016/j.eurpolymj.2020.109908 %T Alkynyl-functionalized chain-extended PCL for coupling to biological molecules %U https://doi.org/10.1016/j.eurpolymj.2020.109908 %X Chemical functionalization of poly(ε-caprolactone) (PCL) enables a molecular integration of additional function. Here, we report an approach to incorporate reactive alkynyl side-groups by synthesizing a chain-extended PCL, where the reactive site is introduced through the covalently functionalizable chain extender 3-(prop-2-yn-1-yloxy)propane-1,2-diol (YPD). Chain-extended PCL with Mw of 101 to 385 kg·mol−1 were successfully synthesized in a one-pot reaction from PCL-diols with various molar masses, L-lysine ethyl ester diisocyanate (LDI) or trimethyl(hexamethylene)diisocyanate (TMDI), and YPD, in which the density of functionalizable groups and spacing between them can be controlled by the composition of the polymer. The employed diisocyanate compounds and YPD possess an asymmetric structure and form a non-crystallizable segment leaving the PCL crystallites to dominate the material’s mechanical properties. The mixed glass transition temperature Tg = −60 to −46 °C of the PCL/polyurethane amorphous phase maintains the synthesized materials in a highly elastic state at ambient and physiological conditions. Reaction conditions for covalent attachment in copper(I)-catalyzed azide-alkyne-cycloaddition reactions (CuAAC) in solution were optimized in a series of model reactions between the alkyne moieties of the chain-extended PCL and benzyl azide, reaching conversions over 95% of the alkyne moieties and with yields of up to 94% for the purified functionalized PCL. This methodology was applied for reaction with the azide-functionalized cell adhesion peptide GRGDS. The required modification of the peptide provides selectivity in the coupling reactions. The obtained results suggest that YPD could potentially be employed as versatile molecular unit for the creation of a variety of functionalizable polyesters as well as polyurethanes and polycarbonates offering efficient and selective click-reactions. %0 journal article %@ 1616-5187 %A Löwenberg, C.,Tripodo, G.,Julich-Gruner, K.,Neffe, A.,Lendlein, A. %D 2020 %J Macromolecular Bioscience %N 10 %P 2000221 %R doi:10.1002/mabi.202000221 %T Supramolecular Gelatin Networks Based on Inclusion Complexes %U https://doi.org/10.1002/mabi.202000221 10 %X Hydrogel forming physical networks based on gelatin are an attractive approach toward multifunctional biomaterials with the option of reshaping, self‐healing, and stimuli‐sensitivity. However, it is challenging to design such gelatin‐based hydrogels to be stable at body temperature. Here, gelatin functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) side chains is crosslinked with cyclodextrin (CD) dimers under formation of inclusions complexes. The supramolecular networks displayed at room temperature decreased water uptake (200–600 wt% for DAT‐based systems, 200 wt% for DATT based systems), and increased storage moduli up to 25.6 kPa determined by rheology compared to DAT(T) gelatin. The gel–sol transition temperature increased from 33 up to 42 °C. The presented system that is completely based on natural building blocks may form the basis for materials that may potentially respond by dissolution or changes of properties to changes in environmental conditions or to the presence of CD guest molecules. %0 journal article %@ 1042-7147 %A Luetzow, K.,Hommes-Schattmann, P.J.,Neffe, A.T.,Ahmad, B.,Williams, G.R.,Lendlein, A. %D 2019 %J Polymers for Advanced Technologies %N 5 %P 1165-1172 %R doi:10.1002/pat.4331 %T Perfluorophenyl azide functionalization of electrospun poly(para-dioxanone) %U https://doi.org/10.1002/pat.4331 5 %X Strategies to surface‐functionalize scaffolds by covalent binding of biologically active compounds are of fundamental interest to control the interactions between scaffolds and biomolecules or cells. Poly(para‐dioxanone) (PPDO) is a clinically established polymer that has shown potential as temporary implant, eg, for the reconstruction of the inferior vena cava, as a nonwoven fiber mesh. However, PPDO lacks suitable chemical groups for covalent functionalization. Furthermore, PPDO is highly sensitive to hydrolysis, reflected by short in vivo half‐life times and degradation during storage. Establishing a method for covalent functionalization without degradation of this hydrolyzable polymer is therefore important to enable the surface tailoring for tissue engineering applications. It was hypothesized that treatment of PPDO with an N‐hydroxysuccinimide ester group bearing perfluorophenyl azide (PFPA) under UV irradiation would allow efficient surface functionalization of the scaffold. X‐ray photoelectron spectroscopy and attenuated total reflectance Fourier‐transformed infrared spectroscopy investigation revealed the successful binding, while a gel permeation chromatography study showed that degradation did not occur under these conditions. Coupling of a rhodamine dye to the N‐hydroxysuccinimide esters on the surface of a PFPA‐functionalized scaffold via its amine linker showed a homogenous staining of the PPDO in laser confocal microscopy. The PFPA method is therefore applicable even to the surface functionalization of hydrolytically labile polymers, and it was demonstrated that PFPA chemistry may serve as a versatile tool for the (bio‐)functionalization of PPDO scaffolds. %0 conference poster %@ %A Folikumah, M.,Neffe, A.,Behl, M.,Lendlein, A. %D 2019 %J Advanced Functional Polymers for Medicine (AFPM) 2019 %N %P %T Thiol-Michael reactions of optically-active mercapto-acids in aqueous medium %U %X %0 conference poster %@ %A Folikumah, M.,Neffe, A.,Behl, M.,Lendlein, A. %D 2019 %J Polydays 2019 - Polymer Science and Engineering in View of Digitalization %N %P %T Thiol-Michael reactions of optically active mercapto-acids in aqueous medium %U %X %0 journal article %@ 2059-8521 %A Folikumah, M.,Neffe, A.,Behl, M.,Lendlein, A. %D 2019 %J MRS Advances %N 46 - 47 %P 2515-2525 %R doi:10.1557/adv.2019.308 %T Thiol Michael-Type Reactions of Optically Active Mercapto-Acids in Aqueous Medium %U https://doi.org/10.1557/adv.2019.308 46 - 47 %X Defined chemical reactions in a physiological environment are a prerequisite for the in situ synthesis of implant materials potentially serving as matrix for drug delivery systems, tissue fillers or surgical glues. ‘Click’ reactions like thiol Michael-type reactions have been successfully employed as bioorthogonal reaction. However, due to the individual stereo-electronic and physical properties of specific substrates, an exact understanding their chemical reactivity is required if they are to be used for in-situ biomaterial synthesis. The chiral (S)-2-mercapto-carboxylic acid analogues of L-phenylalanine (SH-Phe) and L-leucine (SH-Leu) which are subunits of certain collagenase sensitive synthetic peptides, were explored for their potential for in-situ biomaterial formation via the thiol Michael-type reaction.,In model reactions were investigated the kinetics, the specificity and influence of stereochemistry of this reaction. We could show that only reactions involving SH-Leu yielded the expected thiol-Michael product. The inability of SH-Phe to react was attributed to the steric hindrance of the bulky phenyl group. In aqueous media, successful reaction using SH-Leu is thought to proceed via the sodium salt formed in-situ by the addition of NaOH solution, which was intented to aid the solubility of the mercapto-acid in water. Fast reaction rates and complete acrylate/maleimide conversion were only realized at pH 7.2 or higher suggesting the possible use of SH-Leu under physiological conditions for thiol Michael-type reactions. This method of in-situ formed alkali salts could be used as a fast approach to screen mercapto-acids for thio Michael-type reactions without the synthesis of their corresponding esters. %0 journal article %@ 0168-3659 %A Brunacci, N.,Neffe, A.,Wischke, C.,Naolou, T.,Nöchel, U.,Lendlein, A. %D 2019 %J Journal of Controlled Release %N %P 146-156 %R doi:10.1016/j.jconrel.2019.03.004 %T Oligodepsipeptide (nano)carriers: Computational design and analysis of enhanced drug loading %U https://doi.org/10.1016/j.jconrel.2019.03.004 %X High drug loads of nanoparticles are essential to efficiently provide a desired dosage in the required timeframe, however, these conditions may not be reached with so far established degradable matrices. Our conceptual approach for increasing the drug load is based on strengthening the affinity between drug and matrix in combination with stabilizing drug-matrix-hybrids through strong intermolecular matrix interactions. Here, a method for designing such complex drug-matrix hybrids is introduced employing computational methods (molecular dynamics and docking) as well as experimental studies (affinity, drug loading and distribution, drug release from films and nanoparticles). As model system, dexamethasone (DXM), relevant for the treatment of inflammatory diseases, in combination with poly[(rac-lactide)-co-glycolide] (PLGA) as standard degradable matrix or oligo[(3-(S)-sec-butyl)morpholine-2,5-dione]diol (OBMD) as matrix with hypothesized stronger interaction with DXM were investigated. Docking studies predicted higher affinity of DXM to OBMD than PLGA and displayed amide bond participation in hydrogen bonding with OBMD. Experimental investigations on films and nanoparticles, i.e. matrices of different shapes and sizes, confirmed this phenomenon as shown e.g. by a ~10 times higher solid state solubility of DXM in OBMD than in PLGA. DXM-loaded particles of ~ 150 nm prepared by nanoprecipitation in aqueous environment had a drug loading (DL) up to 16 times higher when employing OBMD as matrix compared to PLGA carriers due to enhanced drug retention in the OBMD phase. Importantly, drug relase periods were not altered as the release from films and particles was mainly ruled by the diffusion length as well as matrix degradation rather than the matrix type, which can be assigned to water diffusing into the matrix and breaking up of drug-matrix hydrogen bonds. Overall, the presented design and fabrication scheme showed predictive power and might universally enable the screening of drug/matrix interactions particularly to expand the oligodepsipeptide platform technology, e.g. by varying the depsipeptide side chains, for drug carrier and release systems. %0 journal article %@ 2373-9878 %A Hauser, S.,Wodtke, R.,Tondera, C.,Wodtke, J.,Neffe, A.,Hampe, J.,Lendlein, A.,Löser, R.,Pietzsch, J. %D 2019 %J ACS Biomaterials Science & Engineering %N 11 %P 5979-5989 %R doi:10.1021/acsbiomaterials.9b01299 %T Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials %U https://doi.org/10.1021/acsbiomaterials.9b01299 11 %X Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial–tissue interactions due to its presence and versatile functions in the extracellular environment. TGase 2 catalyzes the cross-linking of proteins through its Ca2+-dependent acyltransferase activity. Moreover, it enhances the interactions between fibronectin and integrins, which in turn mediates the adhesion, migration, and motility of the cells. TGase 2 is also a key player in the pathogenesis of fibrosis. In this study, we investigated whether TGase 2 is present at the biomaterial–tissue interface and might serve as an informative biomarker for the visualization of tissue response toward gelatin-based biomaterials. Two differently cross-linked hydrogels were used, which were obtained by the reaction of gelatin with lysine diisocyanate ethyl ester. The overall expression of TGase 2 by endothelial cells, macrophages, and granulocytes was partly influenced by contact to the hydrogels or their degradation products, although no clear correlation was evidenced. In contrast, the secretion of TGase 2 differed remarkably between the different cells, indicating that it might be involved in the cellular reaction toward gelatin-based hydrogels. The hydrogels were implanted subcutaneously in immunocompetent, hairless SKH1-Elite mice. Ex vivo immunohistochemical analysis of tissue sections over 112 days revealed enhanced expression of TGase 2 around the hydrogels, in particular at days 14 and 21 post-implantation. The incorporation of fluorescently labeled cadaverine derivatives for the detection of active TGase 2 was in accordance with the results of the expression analysis. The presence of an irreversible inhibitor of TGase 2 led to attenuated incorporation of the cadaverines, which verified the catalytic action of TGase 2. Our in vitro and ex vivo results verified TGase 2 as a potential biomarker for tissue response toward gelatin-based hydrogels. In vivo, no TGase 2 activity was detectable, which is mainly attributed to the unfavorable physicochemical properties of the cadaverine probe used. %0 journal article %@ 2296-2646 %A Naolou, T.,Lendlein, A.,Neffe, A.T. %D 2019 %J Frontiers in Chemistry %N %P 346 %R doi:10.3389/fchem.2019.00346 %T Amides as Non-polymerizable Catalytic Adjuncts Enable the Ring-Opening Polymerization of Lactide With Ferrous Acetate Under Mild Conditions %U https://doi.org/10.3389/fchem.2019.00346 %X Sn-based catalysts are effective in the ring-opening polymerization (ROP) but are toxic. Fe(OAc)2 used as an alternative catalyst is suitable for the ROP of lactide only at higher temperatures (>170°C), associated with racemization. In the ROP of ester and amide group containing morpholinediones with Fe(OAc)2 to polydepsipeptides at 135°C, ester bonds were selectively opened. Here, it was hypothesized that ROP of lactones is possible with Fe(OAc)2 when amides are present in the reactions mixture as Fe-ligands could increase the solubility and activity of the metal catalytic center. The ROP of lactide in the melt with Fe(OAc)2 is possible at temperatures as low as 105°C, in the presence of N-ethylacetamide or N-methylbenzamide as non-polymerizable catalytic adjuncts (NPCA), with high conversion (up to 99 mol%) and yield (up to 88 mol%). Polydispersities of polylactide decreased with decreasing reaction temperature to ≤ 1.1. NMR as well as polarimetric studies showed that no racemization occurred at reaction temperatures ≤145°C. A kinetic study demonstrated a living chain-growth mechanism. MALDI analysis revealed that no side reactions (e.g., cyclization) occurred, though transesterification took place. %0 journal article %@ 1742-7061 %A Sarem, M.,Arya, N.,Heizmann, M.,Neffe, A.,Barbero, A.,Gebauer, T.,Martin, I.,Lendlein, A.,Shastri, V. %D 2018 %J Acta Biomaterialia %N %P 83-94 %R doi:10.1016/j.actbio.2018.01.025 %T Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo %U https://doi.org/10.1016/j.actbio.2018.01.025 %X The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineered ArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with the de novo formation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. %0 conference lecture %@ %A Papagrigorakes, M.,Chirico, N.,Blocki, A.,Neffe, A.T.,Jung, F.,Ma, N.,Lendlein, A. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T AD-MSCS change their morphology and secretion profile as a response to changes in substrates`elastic properties in combination with inflammatory stimuli %U %X %0 conference lecture %@ %A Lendlein, A.,Neffe, A.T. %D 2018 %J 2nd International Conference on Dermal Delivery by Nanocarriers: Highlights from SFB 1112, Abschlusscolloquium %N %P %T Depsipeptides - An innovative nanocarrier system %U %X %0 journal article %@ 0014-3057 %A Piluso, S.,Vukicevic, R.,Noechel, U.,Braune, S.,Lendlein, A.,Neffe, A. %D 2018 %J European Polymer Journal %N %P 77-85 %R doi:10.1016/j.eurpolymj.2018.01.017 %T Sequential alkyne-azide cycloadditions for functionalized gelatin hydrogel formation %U https://doi.org/10.1016/j.eurpolymj.2018.01.017 %X While click chemistry reactions for biopolymer network formation are attractive as the defined reactions may allow good control of the network formation and enable subsequent functionalization, tailoring of gelatin network properties over a wide range of mechanical properties has yet to be shown. Here, it is demonstrated that copper-catalyzed alkyne-azide cycloaddition of alkyne functionalized gelatin with diazides gave hydrogel networks with properties tailorable by the ratio of diazide to gelatin and diazide rigidity. 4,4′-diazido-2,2′-stilbenedisulfonic acid, which has been used as rigid crosslinker, yielded hydrogels with Young’s moduli E of 50–390 kPa and swelling degrees Q of 150–250 vol.%, while the more flexible 1,8-diazidooctane resulted in hydrogels with E = 125–280 kPa and Q = 225–470 vol.%. Storage moduli could be varied by two orders of magnitude (G′ = 100–20,000 Pa). An indirect cytotoxicity test did not show cytotoxic properties. Even when employing 1:1 ratios of alkyne and azide moieties, the hydrogels were shown to contain both, unreacted alkyne groups on the gelatin backbone as well as dangling chains carrying azide groups as shown by reaction with functionalized fluorescein. The free groups, which can be tailored by the employed ratio of the reactants, are accessible for covalent attachment of drugs, as was demonstrated by functionalization with dexamethasone. The sequential network formation and functionalization with click chemistry allows access to multifunctional materials relevant for medical applications. %0 journal article %@ 1042-7147 %A Piluso, S.,Lendlein, A.,Neffe, A.T. %D 2017 %J Polymers for Advanced Technologies %N 10 %P 1318-1324 %R doi:10.1002/pat.3962 %T Enzymatic action as switch of bulk to surface degradation of clicked gelatin-based networks %U https://doi.org/10.1002/pat.3962 10 %X Polymer degradation occurs under physiological conditions in vitro and in vivo, especially when bonds susceptible to hydrolysis are present in the polymer. Understanding of the degradation mechanism, changes of material properties over time, and overall rate of degradation is a necessary prerequisite for the knowledge-based design of polymers with applications in biomedicine. Here, hydrolytic degradation studies of gelatin-based networks synthesized by copper-catalyzed azide-alkyne cycloaddition reaction are reported, which were performed with or without addition of an enzyme. In all cases, networks with a stilbene as crosslinker proofed to be more resistant to degradation than when an octyl diazide was used. Without addition of an enzyme, the rate of degradation was ruled by the crosslinking density of the network and proceeded via a bulk degradation mechanism. Addition of Clostridium histolyticum collagenase resulted in a much enhanced rate of degradation, which furthermore occurred via surface erosion. The mesh size of the hydrogels (>7 nm) was in all cases larger than the hydrodynamic radius of the enzyme (4.5 nm) so that even in very hydrophilic networks with large mesh size enzymes may be used to induce a fast surface degradation mechanism. This observation is of general interest when designing hydrogels to be applied in the presence of enzymes, as the degradation mechanism and material performance are closely interlinked. %0 conference lecture %@ %A Zou, J.,Wang, W.,Neffe, A.T.,Xu, X.,Li, Z.,Deng, Z.,Sun, X. Ma, N.,Lendlein, A. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel) %U %X %0 journal article %@ 1386-0291 %A Zou, J.,Wang, W.,Neffe, A.T.,Xu, X.,Li, Z.,Deng, Z.,Sun, X. Ma, N.,Lendlein, A. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 297-307 %R doi:10.3233/CH-179210 %T Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel) %U https://doi.org/10.3233/CH-179210 3-4 %X Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840±120 μm after 4 days, and distributed in the whole scaffold (2 mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55±0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93±1%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration. %0 journal article %@ 1386-0291 %A Blocki, A.,Loeper, F.,Chirico, N.,Neffe, A.T.,Jung, F.,Stamm, C.,Lendlein, A. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 251-259 %R doi:10.3233/CH-179206 %T Engineering of cell-laden gelatin-based microcapsules for cell delivery and immobilization in regenerative therapies %U https://doi.org/10.3233/CH-179206 3-4 %X Cell-based therapies often face the challenge of low cell retention and viability upon transplantation. Hence, biomaterials, which can immobilize transplanted cells, while at the same time support cell viability, are essential for successful clinical application. Noteworthy, biomaterials in the micrometer range such as microcapsules have the advantage of a minimally invasive introduction into tissue.,Hence, we established an approach to generate gelatin-based cell carriers in the form of microspherical hydrogels. Fibroblasts were microencapsulated in glycidylmethacrylate (GMA)-functionalized gelatin by photopolymerization. While the degree of GMA-functionalization was kept constant, the hydrogel cross-linking density was adjusted by varying the time of irradiation, or the average gelatin-chain length.,Stable microcapsules could be achieved with 10 wt% GMA-gelatin solutions for all irradiation periods tested (0.5 –2 min). Evaluation of cell viability revealed that microgels with the same weight content of biopolymer but with decreased cross-linking densities and thus decreasing storage, and E moduli resulted in best cell support. Noteworthy, encapsulated cells partially migrated out of the microcapsules and attached to the spherical surface.,10 wt% GMA-gelatin-based hydrogels with E moduli properties comparable to the native cellular niche proved to be a promising biomaterial suitable for the production of cell-laden microcapsules and shall be evaluated further for biomedical application. %0 journal article %@ 1042-7147 %A Blocki, A.,Loewenberg, C.,Jiang, Y.,Kratz, K.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2017 %J Polymers for Advanced Technologies %N 10 %P 1245-1251 %R doi:10.1002/pat.3947 %T Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties %U https://doi.org/10.1002/pat.3947 10 %X Gelatin-based hydrogels offer various biochemical cues that support encapsulated cells and are therefore suitable as cell delivery vehicles in regenerative medicine. However, besides the biochemical signals, biomechanical cues are crucial to ensure an optimal support of encapsulated cells. Hence, we aimed to correlate the cellular response of encapsulated cells to macroscopic and microscopic elastic properties of glycidylmethacrylate (GMA)-functionalized gelatin-based hydrogels. To ensure that different observations in cellular behavior could be attributed to differences in elastic properties, an identical concentration as well as degree of functionalization of biopolymers was utilized to form covalently crosslinked hydrogels. Elastic properties were merely altered by varying the average gelatin-chain length. Hydrogels exhibited an increased degree of swelling and a decreased bulk elastic modulus G′ with prolonged autoclaving of the starting solution. This was accompanied by an increase of hydrogel mesh size and thus by a reduction of crosslinking density. Tougher hydrogels retained the largest amount of cells; however, they also interfered with cell viability. Softer gels contained a lower cell density, but supported cell elongation and viability. Observed differences could be partially attributed to differences in bulk properties, as high crosslinking densities interfere with diffusion and cell spreading and thus can impede cell viability. Interestingly, a microscopic elastic modulus in the range of native soft tissue supported cell viability and elongation best while ensuring a good cell entrapment. In conclusion, gelatin-based hydrogels providing a soft tissue-like microenvironment represent adequate cell delivery vehicles for tissue engineering approaches. %0 journal article %@ 1042-7147 %A Hommes-Schattmann, P.J.,Neffe, A.T.,Ahmad, B.,Williams, G.R.,M´Bele, G.,Vanneaux, V.,Menasche, P.,Kalfa, D.,Lendlein, A. %D 2017 %J Polymers for Advanced Technologies %N 10 %P 1312-1317 %R doi:10.1002/pat.3963 %T RGD constructs with physical anchor groups as polymer co-electrospinnable cell adhesives %U https://doi.org/10.1002/pat.3963 10 %X The tissue integration of synthetic polymers can be promoted by displaying RGD peptides at the biointerface with the objective of enhancing colonization of the material by endogenous cells. A firm but flexible attachment of the peptide to the polymer matrix, still allowing interaction with receptors, is therefore of interest. Here, the covalent coupling of flexible physical anchor groups, allowing for temporary immobilization on polymeric surfaces via hydrophobic or dipole–dipole interactions, to a RGD peptide was investigated. For this purpose, a stearate or an oligo(ethylene glycol) (OEG) was attached to GRGDS in 51–69% yield. The obtained RGD linker constructs were characterized by NMR, IR and MALDI-ToF mass spectrometry, revealing that the commercially available OEG and stearate linkers are in fact mixtures of similar compounds. The RGD linker constructs were co-electrospun with poly(p-dioxanone) (PPDO). After electrospinning, nitrogen could be detected on the surface of the PPDO fibers by X-ray photoelectron spectroscopy. The nitrogen content exceeded the calculated value for the homogeneous material mixture suggesting a pronounced presentation of the peptide on the fiber surface. Increasing amounts of RGD linker constructs in the electrospinning solution did not lead to a detection of an increased amount of peptide on the scaffold surface, suggesting inhomogeneous distribution of the peptide on the PPDO fiber surface. Human adipose-derived stem cells cultured on the patches showed similar viability as when cultured on PPDO containing pristine RGD. The fully characterized RGD linker constructs could serve as valuable tools for the further development of tissue-integrating polymeric scaffolds. %0 journal article %@ 0939-6411 %A Zhang, N.,Said, A.,Wischke, C.,Kral, V.,Brodwolf, R.,Volz, P.,Boreham, A.,Gerecke, C.,Li, W.,Neffe, A.T.,Kleuser, B.,Alexiev, U.,Lendlein, A.,Schaefer-Korting, M. %D 2017 %J European Journal of Pharmaceutics and Biopharmaceutics %N %P 66-75 %R doi:10.1016/j.ejpb.2016.10.019 %T Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles – Composition-dependent skin penetration enhancement of a dye probe and biocompatibility %U https://doi.org/10.1016/j.ejpb.2016.10.019 %X Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1% and particle size ranged from 35 to 244 nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. %0 journal article %@ 0939-6411 %A Brunacci, N.,Wischke, C.,Naolou, T.,Neffe, A.T.,Lendlein, A. %D 2017 %J European Journal of Pharmaceutics and Biopharmaceutics %N %P 61-65 %R doi:10.1016/j.ejpb.2016.11.011 %T Influence of surfactants on depsipeptide submicron particle formation %U https://doi.org/10.1016/j.ejpb.2016.11.011 %X Surfactants are required for the formation and stabilization of hydrophobic polymeric particles in aqueous environment. In order to form submicron particles of varying sizes from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diols ((OBMD)-diol), different surfactants were investigated. As new surfactants, four-armed star-shaped oligo(ethylene glycol)s of molecular weights of 5–20 kDa functionalized with desamino-tyrosine (sOEG-DAT) resulted in smaller particles with lower PDI than with desaminotyrosyl tyrosine (sOEG-DATT) in an emulsion/solvent evaporation method. In a second set of experiments, sOEG-DAT of Mn = 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-α-tocopherol polyethylene glycol succinate (VIT E-TPGS) for OBMD particle preparation. sOEG-DAT allowed to systematically change sizes in a range of 300 up to 900 nm with narrow polydispersity, while in the other cases, a lower size range (250–400 nm, PVA; ∼300 nm, Tween 20) or no effective particle formation was observed. The ability of tailoring particle size in a broad range makes sOEG-DAT of particular interest for the formation of oligodepsipeptide particles, which can further be investigated as drug carriers for controlled delivery. %0 lecture %@ %A Lendlein, A.,Schroeter, M.,Schulz, B.,Neffe, A.T. %D 2017 %J %N %P %T Wahlpflicht Polymerchemie – Anwendungen in der Medizin Resorbierbare Polymere %U %X %0 book part %@ %A Lendlein, A.,Razzaq, M.Y.,Wischke, C.,Kratz, K.,Heuchel, M.,Zotzmann, J.,Hiebl, B.,Neffe, A.T.,Behl, M. %D 2017 %J Comprehensive Biomaterials II - Reference Module in Materials Science and Materials Engineering, Metallic, Ceramic, and Polymeric Biomaterials %N %P 620-647 %R doi:10.1016/B978-0-12-803581-8.10213-9 %T Shape-Memory Polymers %U https://doi.org/10.1016/B978-0-12-803581-8.10213-9 %X This is an update of A. Lendlein, C. Wischke, K. Kratz, M. Heuchel, J. Zotzmann, B. Hiebl, A.T. Neffe and M. Behl, 1.126 – Shape-Memory Polymers. In Comprehensive Biomaterials, edited by Paul Ducheyne, Elsevier, Oxford, 2011, pp. 479–496.,Medical devices such as implants, surgical instruments, extracorporal devices, and wound covers, as well as controlled drug delivery systems (CDDS) require a specific combination of material properties and functions including, for example, mechanical stability, biocompatibility, and biofunctionality. Polymeric biomaterials are of high relevance for such applications, as properties and functions can be tuned in a wide range by only small defined variations of their chemical or morphological structure. The rapid progress in surgical techniques, especially in minimally invasive surgery, requires smart materials, which are capable of an active on-demand movement and which do not need to be removed in a second surgery. These challenges can be addressed by shape-memory polymers (SMPs) described in this chapter. SMPs are of high technological significance for biomedical applications as they enable on-demand predefined changes in the shape of a device upon exposure to a suitable stimulus such as heat or alternating magnetic field (AMF). Multifunctional materials are obtained when the shape-memory effect is combined with an additional function such as hydrolytic degradability, biofunctionality, and controlled drug release. Selected biomaterials with shape-memory capability are presented, including data on their biocompatibility. The potential of SMPs as a platform technology for biomedical applications is sketched by an overview on SMP-based medical devices being developed and the potential use of SMPs as matrix for CDDS. %0 journal article %@ 0142-9612 %A Lohmann, P.,Willuweit, A.,Neffe, A.T.,Geisler, S.,Gebauer, T.P.,Beer, S.,Coenen, H.H.,Fischer, H.,Hermanns-Sachweh, B.,Lendlein, A.,Shah, N.J.,Kiessling, F.,Langen, K.-J. %D 2017 %J Biomaterials %N %P 158-169 %R doi:10.1016/j.biomaterials.2016.10.039 %T Bone regeneration induced by a 3D architectured hydrogel in a rat critical-size calvarial defect %U https://doi.org/10.1016/j.biomaterials.2016.10.039 %X Bone regeneration can be stimulated by implantation of biomaterials, which is especially important for larger bone defects. Here, healing potency of the porous ArcGel was evaluated in a critical-size calvarial bone defect in rats in comparison with clinical standard autologous bone and Bio-Oss® Collagen (BioOss), a bone graft material frequently used in clinics. Bone healing and metabolic processes involved were monitored longitudinally by [18F]-fluoride and [18F]-FDG μ-PET/CT 1d, 3d, 3w, 6w, and 12w post implantation. Differences in quality of bone healing were assessed by ex vivo μ-CT, mechanical tests and histomorphometry. The amount of bone formed after implantation of ArcGel was comparable to autologous bone and superior to BioOss (histomorphometry). Furthermore, microarchitecture of newly formed bone was more physiological and better functional in case of ArcGel (push-out tests). [18F]-FDG uptake increased until 3d after implantation, and decreased until 12w for both ArcGel and BioOss. [18F]-fluoride uptake increased until 3w post implantation for all materials, but persisted significantly longer at higher levels for BioOss, which indicates a prolonged remodelling phase. The study demonstrates the potential of ArcGel to induce restitutio ad integrum comparable with clinical standard autologous bone and better bone regeneration in large defects compared to a commercial state-of-the-art biomaterial. %0 conference lecture %@ %A Blocki, A.,Loeper, F.,Chirico, N.,Neffe, A.T.,Jung, F.,Stamm, C.,Lendlein, A. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Engineering of cell-laden gelatin-based microcapsules for cell delivery and immobilization in regenerative therapies %U %X %0 journal article %@ 1525-7797 %A Wang, W.,Naolou, T.,Ma, N.,Deng, Z.,Xu, X.,Mansfeld, U.,Wischke, C.,Gossen, M.,Neffe, A.T.,Lendlein, A. %D 2017 %J Biomacromolecules %N 11 %P 3819-3833 %R doi:10.1021/acs.biomac.7b01034 %T Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells %U https://doi.org/10.1021/acs.biomac.7b01034 11 %X The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an Mn ∼ 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60–150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells. %0 conference lecture %@ %A Neffe, A.,Piluso, S.,Lendlein, A. %D 2017 %J Polymers for Advanced Technologies Conference 2017 %N %P %T Clicked gelatin hydrogels - Multifunctional networks showing enzymatic surface degradation %U %X %0 conference poster %@ %A Hommes-Schattmann, P.,Neffe, A.,Zierke, M.,Lendlein, A. %D 2017 %J XXVI International Materials Research Congress (IMRC) 2017; Symp. F4: Shape-memory and self-repairing materials %N %P %T Polyester urethanes with multiblock sequence structure and alkynyl-functionalized side chains %U %X Thermoplastic polyester urethanes (TPU) are typically synthesized by,copolymerization of dihydroxy-terminated polyester-based “macrodiols” and,diisocyanate components. A second diol component of low molar mass (so called,"chain extenders") may be added to the polymerization to increase the overall,molecular weight of the TPU and to form oligourethane segments. In absence of,functionalized side chains, means for post-functionalization of the TPU backbone are,limited and often non-specific. An efficient way to introduce defined motifs for specific,covalent functionalization of the TPU backbone is utilizing chain extenders that bear,non-nucleophilic functional side chains. A structurally simple alkynyl-functionalized,diol, 3-(prop-2-yn-1-yloxy)propane-1,2-diol (YPD), is presented as component for the,synthesis of covalently functionalizable polyester urethanes (PEU) with multiblock,sequence structure. YPD can be synthesized in two steps from commercially,available materials on multi-gram scale. PEUs with Mn of 22 to 87 kgꞏmol-1 (GPC,,universal calibration) were successfully synthesized in one pot from dihydroxyterminated,poly(ε-caprolactone) (PCL) with different molecular weights, L-lysine ethyl,ester diisocyanate (LDI) or trimethyl(hexamethylene)diisocyanate (TMDI), and YPD.,1H/13C-NMR spectroscopy confirmed the chemical composition of the materials.,Model reactions to couple azides to the alkyne moieties of the PEUs via copper(I)-,catalyzed azide-alkyne-cycloaddition reactions (CuAAC, “click chemistry”) using,benzyl azide under various conditions were investigated, allowing conversions of,>95% (1H-NMR) of the alkyne moieties with yields of up to 94% for the purified,functionalized PEUs. The optimized conditions (40 °C, THF/t-BuOH/H2O [2.5:2.5:1],as solvent mixture, acetic acid as additive) were employed to successfully couple a,GRGDS-peptide bearing an azide-functionalized aliphatic linker with 50% degree of,functionalization of the polymer. The obtained results show that YPD can serve as,versatile addition to the pool of available diol-components for the synthesis of,functionalized multiblock PEUs, as the alkynyl moieties are highly suitable for further,functionalization, e.g. the coupling of biomolecules under aqueous and fairly mild,conditions. %0 conference lecture %@ %A Brunacci, N.,Wischke, C.,Neffe, A.,Lendlein, A. %D 2017 %J BIFTM PhD Symposium - BioInterfaces in Technology and Medicine %N %P %T Evaluation of surfactants for the formation of sub-micron depsipeptide particles %U %X %0 conference lecture %@ %A Krüger-Genge, A.,Hauser, S.,Neffe, A.,Pietzsch, J.,Lendlein, A.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Endothelialisation of gelatin- based hydrogels with different elasticity and degradation time %U %X %0 conference lecture %@ %A Blocki, A.,Löper, F.,Chirico, N.,Neffe, A.,Jung, F.,Stamm, C.,Lendlein, A. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie %N %P %T Engineering of cell-laden gelatin-based microcapsules for cell delivery and immobilization in cell-based regenerative therapies %U %X %0 conference lecture %@ %A Neffe, A.,Naolou, T.,Lendlein, A. %D 2017 %J MRS Spring Meeting 2017 %N %P %T Influence of metal softness on the ring-opening polymerization of 2;5-morpholinediones and lactones %U %X %0 conference lecture %@ %A Zou, J.,Wang, W.,Neffe, A.,Xu, X.,Li, Z.,Deng, Z.,Sun, X.,Ma, N.,Lendlein, A. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Adipogenic differentiation of human adipose derived mesenychmal stem cells in 3D architectured gelatin-based hydrogels (ArcGel) %U %X %0 journal article %@ 1838-7640 %A Tondera, C.,Hauser, S.,Krueger-Genge, A.,Jung, F.,Neffe, A.T.,Lendlein, A.,Klopfleisch, R.,Steinbach, J.,Neuber, C.,Pietzsch, J. %D 2016 %J Theranostics %N 12 %P 2114-2128 %R doi:10.7150/thno.16614 %T Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice %U https://doi.org/10.7150/thno.16614 12 %X Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue. %0 conference lecture %@ %A Schulz, C.,Vukicevic, R.,Krueger-Genge, A.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J 18th European Conference for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Monolayer formation and shear-resistance of human umbilical vein endothelial cells on gelatin-based hydrogels with tailorable elsticity and degradability %U %X %0 conference poster %@ %A Zhang, N.,Said, A.,Wischke, C.,Kral, V.,Brodwolf, R.,Boreham, A.,Gerecke, C.,Li, W.,Neffe, A.T.,Kleuser, B.,Alexiev, U.,Lendlein, A.,Schaefer-Korting, M. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %N %P %T Composition-dependent skin penetration and toxicity of a series of poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles %U %X %0 conference poster %@ %A Brunacci, N.,Naolou, T.,Neffe, A.T.,Wischke, C.,Lendlein, A. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %N %P %T Evaluation of surfactants for the formation of sub-micron depsipeptide particles %U %X %0 journal article %@ 1386-0291 %A Schulz, C.,Vukicevic, R.,Krueger-Genge, A.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 699-710 %R doi:10.3233/CH-168007 %T Monolayer formation and shear-resistance of human umbilical vein endothelial cells on gelatin-based hydrogels with tailorable elsticity and degradability %U https://doi.org/10.3233/CH-168007 4 %X The formation of a functionally-confluent and shear-resistant endothelial cell monolayer on cardiovascular implants is a promising strategy to prevent thrombogenic processes after implantation. On the basis of existing studies with arterial endothelial cells adhering after two hours on gelatin-based hydrogels in marked higher numbers compared to tissue culture plates, we hypothesize that also venous endothelial cells (HUVEC) should be able to adhere and form an endothelial monolayer on these hydrogels after days. Furthermore, variation of the hydrogel composition, which slightly influences the materials elasticity and even more the degradation behaviour, should have no considerable effect on HUVEC. Therefore, the monolayer formation and shear resistance of HUVEC were explored on two gelatin-based hydrogels differing in their elasticity (Young’s moduli between 35 and 55 kPa) in comparison to a positive control (HUVEC on glass cover slips) and a negative control (HUVEC on glass cover slips activated with interleukin-1β) after 9 days of culturing. HUVEC density after 9 days of culturing under static conditions was lower on the hydrogels compared to both controls (p < 0.05 each). On G10_LNCO8 slightly more EC adhered than on G10_LNCO5. Staining of the actin cytoskeleton and VE-cadherin revealed a pronounced cell-substrate interaction while the cell-cell interaction was comparable to the controls (HUVEC on glass). The secretion of vasoactive and inflammatory mediators did not differ between the hydrogels and the controls. Adherent HUVEC seeded on the hydrogels were able to resist physiological shear forces and the release of cyto- and chemokines in response to the shear forces did not differ from controls (HUVEC on glass). Therefore, both gelatin-based hydrogels are a suitable substrate for EC and a promising candidate for cardiovascular applications. %0 journal article %@ 1386-0291 %A Tzoneva, R.,Uzunova, V.,Apostolova, S.,Krueger-Genge, A.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 941-949 %R doi:10.3233/CH-168040 %T Angiogenic potential of endothelial and tumor cells seeded on gelatin–based hydrogels in response to electrical stimulations %U https://doi.org/10.3233/CH-168040 4 %X Angiogenesis is one of the key processes during development, wound healing and tumor formation. Prerequisite for its existence is the presence of endogenous electrical fields (EFs) generated by active ion transport across polarized epithelia and endothelia, and appearance of the transcellular potentials. During angiogenesis cellular factor as endothelial growth factor (VEGF), synthesis of adhesive proteins and membrane metalloproteinases (MMPs) govern the angiogenic response to different external stimuli as biomaterials interactions and/or exogenous EF. Gelatin-based hydrogels with elasticities comparable to human tissues have shown to influence cell behavior as well as cell attachment, protein synthesis, VEGF and MMP’s production after the application of EF. Gelatin-based matrices with 3 (G10_LNCO3), 5 (G10_LNCO5), and 8 (G10_LNCO8) fold excess of isocyanate groups per mol of amine groups present in gelatin were used. Human umbilical endothelial cells (HUVEC) (Lonza Basel, Switzerland) and highly invasive breast cancer MDA-MB-231 cells (ATCC®HTB-26TM) were used. For an estimation of the amount of VEGF released from cells a commercially available VEGF ELISA (Thermo Fisher Scientific, Germany) kit was used. Fibronectin (FN) enzyme immunoassay (EIA) was used to analyze the secreted amount of FN by cells seeded on the materials. Secreted MMPs were analyzed by zymography. Gelatin-based hydrogels attracted HUVEC adhesion and diminished the adhesion of MDA-MB-231 cells. The applied direct current (DC) EF induced an almost 5–fold increase in VEGF production by HUVEC seeded on gelatin-based hydrogels, while in contrast, the applied EF decreased the production of VEGF by cancer cells. FN synthesis was elevated in HUVEC cells seeded on gelatin-based materials in comparison to FN synthesis by cancer cells. HUVEC seeded on gelatin hydrogels showed an expression mainly of MMP-2. The application of EF increased the production of MMP-2 in HUVEC seeded on gelatin materials. In contrast, for MDA-MB-231 the production of MMPs on gelatin materials was lower compared to control materials. With the application of EF the levels of MMP-9 decreased but MMP-2 expression raised significantly for gelatin materials. Overall, the results showed that studied gelatin materials suppressed attachment of cancerous cells, as well as suppressed their angiogenic potential revealed by decreased VEGF and MMP production. Thus, this study approved gelatin-based hydrogels with proper elasticity characteristics and different degradation behavior as useful matrices for use in vascular tissue regeneration or in restriction of tumor growth after tumor resection. %0 conference lecture %@ %A Schulz, C.,Vukicevic, R.,Krueger-Genge, A.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Cell layer formation and shear-resistance of human endothelial cells on gelatin-based hydrogels with tailorable elasticity %U %X %0 conference lecture %@ %A Tzoneva, R.,Uzunova, V.,Apostolova, S.,Krueger-Genge, A.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Angiogenic potential of endothelial and tumor cells seeded on gelatin–based hydrogels in response to electrical stimulations %U %X %0 journal article %@ 0168-3659 %A Vogt, A.,Wischke, C.,Neffe, A.T.,Ma, N.,Alexiev, U.,Lendlein, A. %D 2016 %J Journal of Controlled Release %N %P 3-15 %R doi:10.1016/j.jconrel.2016.07.027 %T Nanocarriers for drug delivery into and through the skin - Do existing technologies match clinical challenges? %U https://doi.org/10.1016/j.jconrel.2016.07.027 %X The topical application of drug-loaded particles has been explored extensively aiming at a dermal, follicular or transdermal drug delivery. This review summarizes the present state of the field of polymeric nanocarriers for skin application, also covering methodologies to clinically characterize their interaction and penetration in skin in vivo. Furthermore, with a focus on a clinical perspective, a number of questions are addressed: How well are existing nanoparticle systems penetrating the skin? Which functions of new carrier concepts may meet the clinical requirements? To which extend will instrumental imaging techniques provide information on the biological functions of nanocarriers? Which issues have to be addressed for translating experimental concepts into a future clinical application? %0 journal article %@ 1742-7061 %A Federico, S.,Noechel, U.,Loewenberg, C.,Lendlein, A.,Neffe, A.T. %D 2016 %J Acta Biomaterialia %N %P 1-10 %R doi:10.1016/j.actbio.2016.04.018 %T Supramolecular hydrogel networks formed by molecular recognition of collagen and a peptide grafted to hyaluronic acid %U https://doi.org/10.1016/j.actbio.2016.04.018 %X The extracellular matrix (ECM) is a nano-structured, highly complex hydrogel, in which the macromolecules are organized primarily by non-covalent interactions. Here, in a biomimetic approach, the decorin-derived collagen-binding peptide LSELRLHNN was grafted to hyaluronic acid (HA) in order to enable the formation of a supramolecular hydrogel network together with collagen. The storage modulus of a mixture of collagen and HA was increased by more than one order of magnitude (G′ = 157 Pa) in the presence of the HA-grafted peptide compared to a mixture of collagen and HA (G′ = 6 Pa). The collagen fibril diameter was decreased, as quantified using electron microscopy, in the presence of the HA-grafted peptide. Here, the peptide mimicked the function of decorin by spatially organizing collagen. The advantage of this approach is that the non-covalent crosslinks between collagen molecules and the HA chains created by the peptide form a reversible and dynamic hydrogel, which could be employed for a diverse range of applications in regenerative medicine. %0 journal article %@ 2059-8521 %A Vukicevic, R.,Neffe, A.T.,Gebauer, T.,Frank, O.,Schossig, M.,Lendlein, A. %D 2016 %J MRS Advances %N 27 %P 1995-2001 %R doi:10.1557/adv.2016.416 %T Mechanical Properties of Architectured Gelatin-Based Hydrogels on Different Hierarchical Levels %U https://doi.org/10.1557/adv.2016.416 27 %X Preparation of three-dimensionally architectured porous biomaterials can be achieved in a one-step process by stabilizing gelatin with L-lysine diisocyanate ethyl ester (LDI) in water. The reaction of gelatin with LDI in presence of water leads to the formation of oligourea bridges between gelatin molecules and oligourea chains grafted on gelatin. The number and the length of the bridges, as well as of the grafted chains strongly depend on the concentration of the LDI used for the stabilization, and this has huge influence on the mechanical properties of the material on different hierarchical levels. Higher LDI concentrations yield materials with increased deformation resistance in tensile tests due to the higher number of covalent and physical netpoints in the material. However, mechanical properties determined on the micro-level by AFM indentation showed the opposite trend, i.e. a decrease of Young’s modulus with increasing LDI content. This was interpreted by a decreasing number of shorter oligourea bridges between gelatin chains with decreasing LDI content. %0 conference lecture (invited) %@ %A Behl, M.,Neffe, A.,Kratz, K.,Ma, N.,Lendlein, A. %D 2016 %J Medtec Europe %N %P %T Design Principles of Multifunctional Materials Interacting With Cells %U %X %0 editorial %@ 1616-5187 %A Neffe, A.T.,Grijpma, D.W.,Lendlein, A. %D 2016 %J Macromolecular Bioscience %N 12 %P 1743-1744 %R doi:10.1002/mabi.201600419 %T Editorial: Advanced Functional Polymers for Medicine %U https://doi.org/10.1002/mabi.201600419 12 %X No abstract %0 journal article %@ 2059-8521 %A Neffe, A.T.,Federico, S.,Lendlein, A. %D 2016 %J MRS Advances %N 27 %P 1965-1970 %R doi:10.1557/adv.2016.266 %T Secondary Structure of Decorin-Derived Peptides in Solution %U https://doi.org/10.1557/adv.2016.266 27 %X Decorin is a small leucine-rich repeat proteoglycan supporting collagen fibril formation by controlling the rate of collagen fibrillogenesis and fibril dimensions. Peptides derived from the inner surface of decorin have been shown to bind to collagen, while peptides derived from the outer surface do not display such binding affinity. As typical secondary structural elements such as β-sheets and α-helical regions were found in the decorin X-ray crystal structure, here it was investigated by Circular Dichroism (CD) spectroscopy in solution, whether the same structural elements can be found in the derived peptides. Here it is shown that the peptide derived from decorin’s outer surface has the propensity to adopt helical conformation, as it was found in the crystal structure. The results were more pronounced in 80 vol% TFE solution, which led to an increase in the number as well as the length of helices. In contrast, peptides derived from the inner surface had a higher tendency to adopt β-sheet conformation, also in TFE, which corresponds to the conformation of the original sequence in the crystal structure of decorin. This suggests that the peptides derived from decorin adopt the structures present in the native protein. %0 conference poster %@ %A Naolou, T.,Neffe, A.T.,Lendlein, A. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %N %P %T Ring-Opening polymerization of morpholine-2,5-diones by iron(II) acetate and metal alkoxides %U %X %0 book part %@ %A Hudson, I.L.,Leemaqz, S.Y.,Neffe, A.T.,Abell, A.D. %D 2016 %J Artificial Neural Network Modelling - Studies in Computational Intelligence %N %P 161-212 %R doi:10.1007/978-3-319-28495-8_9 %T Classifying calpain inhibitors for the treatment of cataracts: a Self Organising Map (SOM) ANN/KM approach in drug discovery %U https://doi.org/10.1007/978-3-319-28495-8_9 %X Calpain inhibitors are possible therapeutic agents in the treatment of cataracts. These covalent inhibitors contain an electrophilic anchor (“warhead”), an aldehyde that reacts with the active site cysteine. Whilst high throughput docking of,such ligands into high resolution protein structures (e.g. calpain) is a standard computational approach in drug discovery, there is no docking program that consistently achieves low rates of both false positives (FPs) and negatives (FNs) for ligands that react covalently (via irreversible interactions) with the target protein.,Schroedinger’s GLIDE score, widely used to screen ligand libraries, is known to give high false classification, however a two-level Self Organizing Map (SOM) artificial neural network (ANN) algorithm, with KM clustering proved that,the addition of two structural components of the calpain molecule, number hydrogen bonds and warhead distance, combined with GLIDE score (or its partial energy subcomponents) provide a superior predictor set for classification of true molecular binding strength (IC50). SOM ANN/KM significantly reduced the,number of FNs by 64 % and FPs by 26 %, compared to the glide score alone. FPs were shown to be mostly esters and amides plus alcohols and non-classical, and FNs mainly aldehydes and ketones, masked aldehydes and ketones and Michael. %0 conference lecture %@ %A Lendlein, A.,Neffe, A.T.,Ma, N.,Behl, M.,Wischke, C. %D 2016 %J Multifunctional Biomaterials for Medicine, HVI Symposium 2016 %N %P %T Functional Polymers and Carriers Systems %U %X %0 conference poster %@ %A Brunacci, N.,Naolou, T.,Wischke, C.,Neffe, A.,Lendlein, A. %D 2016 %J Polydays 2016 %N %P %T Depsipeptide submicron particles of different sizes as drug delivery systems %U %X %0 conference lecture %@ %A Neffe, A.,Federico, S.,Piluso, S.,Löwenberg, C.,Pierce, B.,Nöchel, U.,Wischke, C.,Lendlein, A. %D 2016 %J Polydays 2016 %N %P %T Design Strategy for the Elucidation of Protein-Protein-Binding Epitopes; and Application of the Derived Peptides in Biomaterials %U %X %0 conference lecture %@ %A Tondera, C.,Ullm, S.,Krüger-Genge, A.,Jung, F.,Gebauer, T.,Neffe, A.,Lendlein, A.,Steinbach, J.,Pietzsch, J. %D 2016 %J World Biomaterials Congress (WBC 2016) %N %P %T Gelatin-based hydrogels as versatile tools for tissue engineering: insights from multimodal imaging in vivo and ex vivo %U %X %0 conference lecture %@ %A Neffe, A.,Pierce, B.,Tronci, G.,Ma, N.,Pittermann, E.,Gebauer, T.,Frank, O.,Schossig, M.,Xu, X.,Willie, B.,Forner, M.,Ellinghaus, A.,Lienau, J.,Duda, G.,Lendlein, A. %D 2016 %J RegMed Forum & 10 Years BCRT %N %P %T One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration %U %X %0 conference poster %@ %A Blocki, A.,Loewenberg, C.,Jiang, Y.,Kratz, K.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J RegMed Forum - 10 Jahre BCRT %N %P %T Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties %U %X %0 conference lecture %@ %A Lendlein, A.,Neffe, A.T.,Ma, N.,Behl, M.,Wischke, C. %D 2016 %J International Conference on Dermal Drug Delivers by Nanocarrierrs, SFB Konferenz %N %P %T Functional Polymers and Carriers Systems %U %X %0 conference poster %@ %A Blocki, A.,Loewenberg, C.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %N %P %T Mechanobiological response of encapsulated cells to a gelatin matrix with varied crosslinking density %U %X %0 conference poster %@ %A Brunacci, N.,Naolou, T.,Wischke, C.,Neumann, F.,Ma, N.,Neffe, A.T.,Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %N %P %T Comparison of particulate carriers for dexamethasone with oligodepsipeptide or OLGA as matrix material %U %X %0 conference poster %@ %A Hommes-Schattmann, P.J.,Neffe, A.T.,Ahmad, B.,Williams, G.R.,Vanneaux, V.,Menasche, P.,Kalfa, D.,Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %N %P %T Electrospun PPDO- Patches With Incorporated RGD Constructs %U %X %0 conference lecture %@ %A Schulz, C.,Krueger-Genge, A.,Vukicevic, R.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Monolayer formation and shear-resistance of human vein endothelial cells on gelatin-based hydrogels with tailorable elasticity and degradability %U %X %0 conference poster %@ %A Neffe, A.T.,Piluso, S.,Vukicevic, R.,Noechel, U.,Braune, S.,Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %N %P %T Sequential Alkyne-Azide Cycloadditions for Functionalized Gelatin Hydrogel Formation %U %X %0 journal article %@ 0014-3057 %A Naolou, T.,Lendlein, A.,Neffe A.T. %D 2016 %J European Polymer Journal %N %P 139-149 %R doi:10.1016/j.eurpolymj.2016.10.011 %T Influence of metal softness on the metal-organic catalyzed polymerization of morpholin-2,5-diones to oligodepsipeptides %U https://doi.org/10.1016/j.eurpolymj.2016.10.011 %X Synthetic access to oligodepsipeptides (ODP), polymers with high potential in biomedicine, is given by the ring-opening polymerization (ROP) of morpholine-2,5-diones (MDs). Classically, the ROP of MDs is mostly conducted by coordination-insertion polymerization using metal-organics as a catalyst e.g. tin(II) di(2-ethyl hexanoate) (Sn(Oct)2). This ROP has been shown to be significantly more difficult to conduct than the corresponding ROP of dilactide, which was related to different electronic properties of the monomers and potential steric crowding. Here, we investigated the ROP of 3-(S)-sec-butylmorpholine-2,5-dione (BMD) by varying the catalyst’s hardness, comparing Sn(Oct)2 with the ethoxides of indium, magnesium, aluminum and iron(III), as well as with iron(II) acetate. The ROP of BMD with Sn(Oct)2 in bulk at 135 °C for 24 h gave ODP with a number-average molecular weight (Mn) = 4.5 kDa. Mg(OEt)2 gave the best results among the other investigated metal ethoxides with ODP of Mn = 4 kDa and a conversion ratio of 57 mol%. On the other hand, high polymerization temperature was needed (160 °C) in the case of In(OEt)3, which resulted in partial degradation, while Al(OEt)3 and Fe(OEt)3 did not result in polymerization. Very effective for the ROP of the studied MD proofed to be Fe(OAc)2, giving OBMD with a Mn = 5.8 kDa, a polydispersity of 1.1, a conversion ratio of 86 mol%, and no racemization. This catalyst likewise performed well in the polymerization of Ser- and Tyr-based MDs. Fe(II) is softer than Sn(II) and may support the ROP by promoting the alkoxide transfer step of the polymerization, while suppressing the formation of unreactive coordination complexes. In contrast, the metal alkoxides investigated were harder than Fe(II) or Sn(II), but had low steric demand. The results suggest that the hardness of the central atom is the key property in the polymerization, while steric considerations are of lower importance. In addition, a synthesis of MDs with protected side chains in improved yields was introduced. This was achieved by in situ formation of an alkyl iodide that is very effective in the ring closing reaction. %0 conference lecture %@ %A Neffe, A. %D 2015 %J i-WING 2015 – Vom Material zur Innovation %N %P %T Biomaterialien quo vadis? Innovative Materialien für die Biomedizin %U %X %0 journal article %@ 1022-1336 %A Vukicevic, R.,Neffe, A.T.,Luetzow, K.,Pierce, B.F.,Lendlein, A. %D 2015 %J Macromolecular Rapid Communications %N 21 %P 1891-1896 %R doi:10.1002/marc.201500311 %T Conditional Ultrasound Sensitivity of Poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] Microgels for Controlled Lipase Release %U https://doi.org/10.1002/marc.201500311 21 %X Triggering the release of cargo from a polymer network by ultrasonication as an external, noninvasive stimulus can be an interesting concept for on-demand release. Here, it is shown that, in pH- and thermosensitive microgels, the ultrasound sensitivity of the polymer network depends on the external conditions. Crosslinked poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] microgels showed a volume phase transition temperature (VPTT) of 25–50 °C, which increases with decreasing pH. Above the VPTT the polymer chains are collapsed, while below VPTT they are extended. Only in the case of maximum observed swelling, where the polymer chains are expanded, the microgels are mechanically fragmented through ultrasonication. In contrast, when the polymer chains are partially collapsed it is not possible to manipulate the microgels by ultrasound. Additionally, the ultrasound-induced on-demand release of wheat germ lipase from the microgels could be demonstrated successfully. The principle of conditional ultrasound sensitivity is likely to be general and can be used for selection of matrix–cargo combinations. %0 journal article %@ 0044-8249 %A Federico, S.,Pierce, B.F.,Piluso, S.,Lendlein, A.,Neffe, A.T. %D 2015 %J Angewandte Chemie %N 37 %P 11131-11135 %R doi:10.1002/ange.201505227 %T Design von Decorin-basierten Peptiden, die an Kollagen I binden, und ihr Potenzial als Adhaesionssequenzen in Biomaterialien %U https://doi.org/10.1002/ange.201505227 37 %X Das Nachbilden der Bindungsepitope von Protein-Protein-Wechselwirkungen mithilfe kleiner Peptide ist wichtig bei der Entwicklung modularer biomimetischer Systeme. Hier beschreiben wir eine Strategie zum Design solcher bioaktiver Peptide, ohne dass Strukturdaten des Proteinkomplexes benötigt werden, und weisen den Effekt der Inkorporierung solcher Adhäsionssequenzen in komplexen Biomaterialsystemen nach. Dazu wurde die hochrepetitive Struktur von Decorin analysiert. Für dessen innere sowie äußere Oberfläche wurden repräsentative Peptide identifiziert und synthetisiert. Nur Peptide auf Basis der inneren Oberfläche binden an Kollagen. Das Peptid mit der höchsten Bindungsaffinität für Kollagen I führte zu einer geringeren Diffusionsgeschwindigkeit eines gekuppelten Farbstoffs in einem Kollagengel. Dimere des Peptids ermöglichten eine physikalische Vernetzung von Kollagen, wodurch der Speichermodul eines Gels stark erhöht werden konnte. Dies belegt das Potenzial der Peptide für das Design von Biomaterialien für die regenerative Medizin. %0 journal article %@ 1946-4274 %A Loewenberg, C.,Julich-Gruner, K.K.,Neffe, A.T.Lendlein, A. %D 2015 %J MRS Online Proceedings Library %N %P 76-81 %R doi:10.1557/opl.2015.491 %T Influence of glycidylmethacrylate functional groups attached to gelatin on the formation and properties of hydrogels %U https://doi.org/10.1557/opl.2015.491 %X Gelatin functionalized with glycidyl methacrylate (GMA) has been shown to allow crosslinking by photopolymerization and metathesis reaction. However, side chain functionalization of gelatin might reduce triple helicalization, which influences mechanical properties of gelatin-based polymer networks. Here, the influence of glycidylmethycrylation of gelatin on the chain organization, swelling, and mechanical properties is investigated by comparing among each other physical gels prepared from GMA-gelatin solutions of different concentrations (5-20 wt.-%) by drying and rehydration. An increase of GMA-gelatin concentration from 5 wt.-% to 20 wt.-% led to an increased density of produced gelatin films and a decreasing water uptake of the films from 1160 wt.-% to 730 wt.-%, while the storage modulus was increasing about one order of magnitude from 440 Pa to 4090 Pa. The relative single and triple helix content was not influenced by the variation of polymer concentration. %0 journal article %@ 0939-6411 %A Mathew, S.,Baudis, S.,Neffe, A.T.,Behl, M.,Wischke, C.,Lendlein, A. %D 2015 %J European Journal of Pharmaceutics and Biopharmaceutics A %N %P 18-26 %R doi:10.1016/j.ejpb.2015.03.025 %T Effect of diisocyanate linkers on the degradation characteristics of copolyester urethanes as potential drug carrier matrices %U https://doi.org/10.1016/j.ejpb.2015.03.025 %X In this study, the effect of three aliphatic diisocyanate linkers, L-lysine diisocyanate ethyl ester (LDI), hexamethylene diisocyanate (HDI), and racemic 2,2,4-/2,4,4-trimethyl hexamethylene diisocyanate (TMDI), on the degradation of oligo[(rac-lactide)-co-glycolide] (64:36 mol%) based polyester urethanes (PEU) was examined. Samples were characterized for their molecular weight, mass loss, water uptake, sequence structure, and thermal and mechanical properties. Compared to non-segmented PLGA, the PEU showed higher water uptake and generally degraded faster. Interestingly, the rate of degradation was not directly correlating with the hydrophilicity of the diisocyanate moieties; instead, competing intra-/intermolecular hydrogen bonds in between urethane moieties appear to substantially decrease the rate of degradation for LDI-derived PEU. By comparing microparticles (μm) and films (mm) as matrices of different dimensions, it was shown that autocatalysis remains a contributor to degradation of the larger-sized PEU matrices as it is typical for non-segmented lactide/glycolide copolymers. The shown capacity of lactide/glycolide-based multiblock copolymers to degrade faster than PLGA and exhibit improved elastic properties could be of interest for medical implants and drug release systems. %0 editorial %@ 1386-0291 %A Lendlein, A.,Neffe, A.T.,Jerome, C. %D 2015 %J Clinical Hemorheology and Microcirculation %N 1 %P 1-2 %R doi:10.3233/CH-151941 %T Editorial: Advanced Functional Polymers in Medicine (AFPM) %U https://doi.org/10.3233/CH-151941 1 %X No abstract %0 journal article %@ 1946-4274 %A Roch, T.,Julich-Gruner, K.K.,Neffe, A.T.,Ma, N.,Leindlein, A. %D 2015 %J MRS Online Proceedings Library %N %P %R doi:10.1557/opl.2015.327 %T Immuno-compatibility of desaminotyrosine and desaminotyrosyl tyrosine functionalized star-shaped oligo(ethylene glycol)s with different molecular weights %U https://doi.org/10.1557/opl.2015.327 %X Polymer-based therapeutic strategies require biomaterials with properties and functions tailored to the demands of specific applications leading to an increasing number of newly designed polymers. For the evaluation of those new materials, comprehensive biocompatibility studies including cyto-, tissue-, and immunocompatibility are essential. Recently, it could be demonstrated that star-shaped amino oligo(ethylene glycol)s (sOEG) with a number average molecular weight of 5 kDa and functionalized with the phenol-derived moieties desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) behave in aqueous solution like surfactants without inducing a substantial cytotoxicity, which may qualify them as solubilizer for hydrophobic drugs in aqueous solution. However, for biomedical applications the polymer solutions need to be free of immunogenic contaminations, which could result from inadequate laboratory environment or contaminated starting material. Furthermore, the materials should not induce uncontrolled or undesired immunological effects arising from material intrinsic properties. Therefore, a comprehensive immunological evaluation as perquisite for application of each biomaterial batch is required. This study investigated the immunological properties of sOEG-DAT(T) solutions, which were prepared using sOEG with number average molecular weights of 5 kDa, 10 kDa, and 20 kDa allowing analyzing the influence of the sOEG chain lengths on innate immune mechanisms. A macrophage-based assay was used to first demonstrate that all DAT(T)-sOEG solutions are free of endotoxins and other microbial contaminations such as fungal products. In the next step, the capacity of the different DAT(T)-functionalized sOEG solutions to induce cytokine secretion and generation of reactive oxygen species (ROS) was investigated using whole human blood. It was observed that low levels of the pro-inflammatory cytokines interleukin(IL)-1β and IL-6 were detected for all sOEG solutions but only when used at concentrations above 250 µg·mL-1. Furthermore, only the 20 kDa sOEG-DAT induced low amounts of ROS-producing monocytes. Conclusively, the data indicate that the materials were not contaminated with microbial products and do not induce substantial immunological adverse effects in vitro, which is a prerequisite for future biological applications. %0 journal article %@ 0935-9648 %A Neffe, A.T.,Pierce, B.F.,Tronci, G.,Ma, N.,Pittermann, E.,Gebauer, T.,Frank, O.,Schossig, M.,Xu, X.,Willie, B.M.,Forner, M.,Ellinghaus, A.,Lienau, J.,Duda, G.N.,Lendlein, A. %D 2015 %J Advanced Materials %N 10 %P 1738-1744 %R doi:10.1002/adma.201404787 %T One Step Creation of Multifunctional 3D Architectured Hydrogels Inducing Bone Regeneration %U https://doi.org/10.1002/adma.201404787 10 %X Structured hydrogels showing form stability and elastic properties individually tailorable on different length scales are accessible in a one-step process. They support cell adhesion and differentiation and display growing pore size during degradation. In vivo experiments demonstrate their efficacy in biomaterial-induced bone regeneration, not requiring addition of cells or growth factors. %0 journal article %@ 2192-2640 %A Neffe, A.T.,Lendlein, A. %D 2015 %J Advanced Healthcare Materials %N 5 %P 642-645 %R doi:10.1002/adhm.201400724 %T Going Beyond Compromises in Multifunctionality of Biomaterials %U https://doi.org/10.1002/adhm.201400724 5 %X Prioritizing one function in biomaterial and biomedical device design goes hand in hand with compromises with respect to other functions. Strategies to overcome the limitations of such an approach for realizing novel fields of biomaterial application are critically evaluated to promote interdisciplinary and integrative research. %0 conference poster %@ %A Neffe, A.,Vukićević, R.,Lützow, K.,Pierce, B.,Lendlein, A. %D 2015 %J 5. Int. Seminar “Advanced Functional Polymers for Medicine (AFPM)” %N %P %T Ultrasound-sensitive microparticles based on poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] %U %X %0 conference poster %@ %A Löwenberg, C.,Julich-Gruner, K.,Neffe, A.,Lendlein, A. %D 2015 %J Advanced Functional Polymers for Medicine (AFPM) %N %P %T Influence of Ions on the Properties of Swollen Gelatin-Based Networks %U %X %0 conference poster %@ %A Tzoneva, R.,Uzunova, V.,Apostolova, S.,Krüger, A.,Neffe, A.,Jung, F.,Lendlein, A. %D 2015 %J 34. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Effect of electrical stimulation on vascular endothelial and tumor cells on angiogenic response %U %X %0 conference poster %@ %A Vuki evi , R.,Neffe, A.,Gebauer, T.,Xu, X.,Ma, N.,Lendlein, A. %D 2015 %J MRS Fall Meeting 2015; Symposium H “Multifunctionality in Polymer-Based Materials; Gels and Interfaces” %N %P %T Mechanical Properties of Architectured Gelatin-Based Hydrogels on Different Hierarchical Levels %U %X %0 conference poster %@ %A Lohmann, P.,Willuweit, A.,Geisler, S.,Gebauer, T.,Neffe, A.,Lendlein, A.,Shah, N.,Langen, K. %D 2015 %J Konferenz der Deutschen Gesellschaft für Nuklearmedizin (DGN) %N %P %T Untersuchung der Knochenregeneration mittels 18F-Fluorid und 18F-FDG mittels Inveon PET/CT im kritischen Knochendefektmodell bei der Ratte %U %X %0 conference lecture (invited) %@ %A Neffe, A.,Federico, S.,Lendlein, A. %D 2015 %J Advanced Functional Polymers for Medicine (AFPM) %N %P %T Strategy for the Computer-assisted Design of Collagen Binding Peptides and their Application in Biomaterial Design %U %X %0 conference lecture %@ %A Neffe, A.,Federico, S.,Lendlein, A. %D 2015 %J MRS Fall Meeting 2015; Symposium H “Multifunctionality in Polymer-Based Materials; Gels and Interfaces” %N %P %T Crosslinking of Collagen Through Molecular Recognition by Biomimetic; Decorin-Derived Peptides %U %X %0 journal article %@ 1946-4274 %A Julich-Gruner, K.K.,Lendlein, A.,Boccaccini, A.R.,Neffe, A.T. %D 2015 %J MRS Online Proceedings Library %N %P 82-87 %R doi:10.1557/opl.2015.492 %T Anisotropic Composites of Desaminotyrosine and Desaminotyrosyl Tyrosine Functionalized Gelatin and Bioactive Glass Microparticles %U https://doi.org/10.1557/opl.2015.492 %X Functionalization of gelatin with desaminotyrosine (DAT) and desamino tyrosyl tyrosine (DATT) has been demonstrated to allow network formation based on non-covalent interactions of the aromatic moieties. Based on the observation that the DAT(T) groups furthermore could interact with hydroxyapatite fillers, here it was investigated whether such interactions of DAT(T) could also be employed to stabilize composites formed by functionalized gelatins and bioactive glass (BG) particles. Because of sedimentation of the BG microparticles during the gelification, anisotropic composites with two distinct layers were formed. The characterization of mechanical properties by tensile tests and rheology showed that all composites of non-functionalized and DAT(T) functionalized gelatins with BG microparticles showed an increased Young’s modulus (E) up to 3 MPa, an increased storage modulus (G’) up to 100 kPa, increased tensile strength (σmax) up to 3.4 MPa, and increased loss modulus (G’’) compared to the pure matrices. As the observed effects were more pronounced in the DAT(T) functionalized gelatins compared to non-functionalized gelatins, and a much increased thermal stability of these composites was found, it is likely that there are binding interactions between the aromatic moieties and the BG microparticles. This effect open opportunities for the further development of this type of gelatin-based composites for bone regeneration applications. %0 journal article %@ 1386-0291 %A Julich-Gruner, K.K.,Roch, T.,Ma, N.,Neffe, A.T.,Lendlein, A. %D 2015 %J Clinical Hemorheology and Microcirculation %N 1 %P 13-23 %R doi:10.3233/CH-151938 %T Synthesis and characterization of star-shaped oligo(ethylene glycol) with tyrosine derived moieties under variation of their molecular weight %U https://doi.org/10.3233/CH-151938 1 %X Desamino tyrosine (DAT) and desamino tyrosyl tyrosine (DATT) can be used to functionalize the end groups of water soluble polymers. The phenolic groups may enable physical interactions by π– π interaction and hydrogen bonds, which might lead to the formation of a hydrogel by physical crosslinking. However, using star-shaped oligo(ethylene glycols) (sOEG) with a molecular weight of 5 kDa for functionalization with DAT or DATT resulted in the formation of surfactants and not in hydrogels.,As the molecular weight of the sOEG polymer chain can have an influence on forming physical cross links, DAT(T)-fuctionalization of sOEGs with higher molecular weight was investigated, the polymers were structurally characterized and for their mechanical properties were evaluated by rheological measurements.,Aqueous solutions of DAT(T)-sOEGs with 10 and 20 kDa showed lower storage and loss moduli compared to unfunctionalized sOEGs indicating also the formation of surfactants. Cell-based assays showed that all sOEG solutions did not impair cell viability and were free of endotoxins, which could otherwise induce uncontrolled immune responses.,Conclusively, our data suggested that the sOEG solutions have surface active properties without inducing unwanted cellular responses, which is required e.g. in pharmaceutical applications to solubilize hydophobic substances. %0 conference poster %@ %A Naolou, T.,Brunacci, N.,Neffe, A.,Lendlein, A. %D 2015 %J MRS Fall Meeting 2015; Symposium H “Multifunctionality in Polymer-Based Materials; Gels and Interfaces” %N %P %T Oligodepsipeptide synthesis and formation of submicron particles thereof %U %X %0 conference lecture %@ %A Krüger, A.,Löwenberg, C.,Neffe, A.,Roch, T.,Schöne, A.,Schroeter, M.,Viszokai, P.,Vuki evi , R.,Lendlein, A. %D 2015 %J Potsdamer Tag der Wissenschaften 2015 %N %P %T Biomaterialien für die Medizin %U %X %0 editorial %@ 2192-2659 %A Lendlein, A.,Neffe, A.T.,Jerome, C. %D 2014 %J Advanced Healthcare Materials %N 12 %P 1939-1940 %T Editorial: Advanced Functional Polymers for Medicine %U 12 %X No abstract %0 conference object %@ 1932-6254 %A Arya, N.,Gebauer, T.P.,Neffe, A.T.,Lendlein, A.,Shastri, V.P. %D 2014 %J Journal of Tissue Engineering and Regenerative Medicine %N S1 %P 207-518 / PP 79 %R doi:10.1002/term.1932 %T Chondrocyte re-differentiation on ethyl lysine diisocyanate cross-linked gelatin based 3-D scaffolds: Application in cartilage tissue engineering %U https://doi.org/10.1002/term.1932 S1 %X No abstract %0 journal article %@ 1022-1360 %A Rijckaert, B.,Neffe, A.T.,Roch, T.,Gebauer, T.,Pierce, B.F.,Goers, J.,Smink, J.J.,Gossen, M.,Lendlein, A.,Leutz, A. %D 2014 %J Macromolecular Symposia %N 1 %P 91-99 %R doi:10.1002/masy.201400147 %T A High Content Screening Assay for Evaluation of Biomaterial-Mediated Cell Fusion Processes %U https://doi.org/10.1002/masy.201400147 1 %X Biomaterials are of increasing importance in regenerative medicine and entail delivery systems in somatic cell therapies, matrices for tissue engineering or tissue regeneration. The evaluation of biomaterial induced biological effects remains a key issue in clinical application. Cell-based assays for potential cytotoxic and immunological responses have been developed but are often inadequate to address cell-type specific responses to biomaterials. To quantitatively monitor attachment, survival, proliferation and fusion-controlled differentiation of osteoclasts (bone resorbing cells), a High Content Screening (HCS) assay has been developed based on osteoclast differentiation of the murine monocytic cell line RAW 264.7. This assay was applied to investigate the influence of degradation products of polymers from gelatin and lysine diisocyanate, which display tailorable mechanical properties and have potential as biomaterials. The data show that the degradation products inhibit formation of multinuclear osteoclasts and suggest a potential support of bone regeneration by suppression of bone resorption. %0 journal article %@ 0044-8249 %A Wei, Q.,Becherer, T.,Angioletti-Uberti, S.,Dzubiella, J.,Wischke, C.,Neffe, A.T.,Lendlein, A.,Ballauff, M.,Haag, R. %D 2014 %J Angewandte Chemie %N 31 %P 8138-8169 %R doi:10.1002/ange.201400546 %T Wechselwirkungen von Proteinen mit Polymerbeschichtungen und Biomaterialien %U https://doi.org/10.1002/ange.201400546 31 %X Die Proteinadsorption gilt als der wichtigste Faktor der Wechselwirkung zwischen polymeren Biomaterialien und Körperflüssigkeiten oder -gewebe. Die Haupteinflussfaktoren auf die Proteinadsorption sind wasservermittelte hydrophobe und Hydratationskräfte sowie elektrostatische Wechselwirkungen. Eine systematische Analyse verschiedener Monolagen führte zur Aufstellung allgemeiner Leitsätze, den sogenannten “Whitesides-Regeln”. Diese Konzepte wurden erfolgreich auf die Entwicklung verschiedener proteinresistenter Oberflächen angewendet und werden kontinuierlich weiterentwickelt, um das Verständnis von Protein-Material-Wechselwirkungen über die bisherigen Grenzen hinaus zu erweitern. Ebenso werden die Theorien zu Proteinadsorptionsmechanismen aufgrund der sich schnell entwickelnden analytischen Technologien fortlaufend verbessert. Ziel dieses Aufsatzes ist die Verbesserung der aufgestellten empirischen Leitlinien im Hinblick auf die theoretischen und analytischen Fortschritte. Dabei werden die aktuellen analytischen Methoden zur Untersuchung mechanistischer Hypothesen und Theorien zu Protein-Oberflächen-Wechselwirkungen besprochen. Ein besonderes Augenmerk liegt auf aktuellen Technologien im Bereich bioinerter und biospezifischer Beschichtungen und ihrer Anwendungen in der Biomedizin. %0 journal article %@ 1022-1360 %A Neffe, A.T.,Santan, H.D.,Kamlage, S.,Gottschalk, B.,Lendlein, A. %D 2014 %J Macromolecular Symposia %N 1 %P 91-97 %R doi:10.1002/masy.201400145 %T Micellization of Aminoterminated Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) in the Presence of Hyaluronic Acid %U https://doi.org/10.1002/masy.201400145 1 %X At concentrations above 15 wt-%, aqueous solutions of mixtures of aminoterminated poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) block copolymers (PEPE) and hyaluronic acid show a reversible sol-gel-transition upon change of temperature. For non-aminoterminated PEPEs, this gel transition could be related to micellization and subsequent colloidal jamming of the micelles. Here, the mechanism of gelation for the aminoterminated compound is investigated by fluorescence spectroscopy and 1H-NMR spectroscopy. The aminoterminated PEPE also form micelles. The onset of micellization is temperature and concentration dependent, and can be tuned to 20–40 °C. Interestingly, with increasing molecular weight of the hyaluronic acid component, the micellization is observed at lower concentrations. %0 journal article %@ 0142-9612 %A Ullm, S.,Krueger, A.,Tondera, C.,Gebauer, T.P.,Neffe, A.T.,Lendlein, A.,Jung, F.,Pietzsch, J. %D 2014 %J Biomaterials %N 37 %P 9755-9766 %R doi:10.1016/j.biomaterials.2014.08.023 %T Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties %U https://doi.org/10.1016/j.biomaterials.2014.08.023 37 %X Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft tissue. %0 conference lecture %@ %A Julich-Gruner, K.K.,Roch, T.,Ma, N.,Neffe, A.T.,Lendlein, A. %D 2014 %J Advanced Functional Polymers for Medicine, AFPM 2014 %N %P %T Synthesis and characterization of star-shaped oligo(ethylene glycol) with tyrosine derived moieties under variation of their molecular weight %U %X %0 conference lecture %@ %A Krueger, A.,Ullm, S.,Gebauer, T.G.,Neffe, A.T.,Pietzsch, J.,Jung, F.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Interaction between human umbilical venous endothelial cell and a gelatin-based hydrogel %U %X %0 journal article %@ 1433-7851 %A Wei, Q.,Becherer, T.,Angioletti-Uberti, S.,Dzubiella, J.,Wischke, C.,neffe, A.T.,Lendlein, A.,Ballauff, M.,Haag, R. %D 2014 %J Angewandte Chemie - International Edition %N 31 %P 8004-8031 %R doi:10.1002/anie.201400546 %T Protein Interactions with Polymer Coatings and Biomaterials %U https://doi.org/10.1002/anie.201400546 31 %X Protein adsorption is considered to be the most important factor of the interaction between polymeric biomaterials and body fluids or tissues. Water-mediated hydrophobic and hydration forces as well as electrostatic interactions are believed to be the major factors of protein adsorption. A systematic analysis of various monolayer systems has resulted in general guidelines, the so-called “Whitesides rules”. These concepts have been successfully applied for designing various protein-resistant surfaces and are being studied to expand the understanding of protein–material interactions beyond existing limitations. Theories on the mechanisms of protein adsorption are constantly being improved due to the fast-developing analytical technologies. This Review is aimed at improving these empirical guidelines with regard to present theoretical and analytical advances. Current analytical methods to test mechanistic hypotheses and theories of protein–surface interactions will be discussed. Special focus will be given to state-of-the-art bioinert and biospecific coatings and their applications in biomedicine. %0 conference poster %@ %A Loewenberg, C.,Julich-Gruner, K.K.,Neffe, A.T,Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %N %P %T Synthesis and Characterization of Polymer Networks Based on Glycidylmethacrylated Gelatin %U %X %0 conference lecture %@ %A Julich-Gruner, K.K.,Lendlein, A.,Boccaccini, A.R.,Neffe, A.T. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %N %P %T Anisotropic Composites of Desaminotyrosine and Desaminotyrosyl Tyrosine Functionalized Gelatin and Bioactive Glass Microparticles %U %X %0 conference lecture %@ %A Loewenberg, C.,Julich-Gruner, K.K.,Neffe, A.T,Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %N %P %T Influence of glycidylmethacrylate functional groups attached to gelatin on the formation and properties of hydrogels %U %X %0 conference lecture %@ %A Roch, T.,Julich-Gruner, K.K.,Neffe, A.T.,Ma, N.,Leindlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit, Symposium B %N %P %T Immuno-compatibility of desaminotyrosine and desaminotyrosyl tyrosine functionalized star-shaped oligo(ethylene glycol)s with different molecular weights %U %X %0 conference lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2014 %J Vortrag im Industriemuseum Teltow %N %P %T Multifunktionale Polymere - Zukunftsperspektiven fuer Materialien in der Medizin %U %X %0 conference lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2014 %J Advanced Functional Polymers for Medicine, AFPM 2014 %N %P %T Biopolymer-based hydrogels and their evaluation as biomaterials %U %X %0 conference poster %@ %A Wischke, C.,Neffe, A.T.,Loebler, M.,Sternberg, K.,Stachs, O.,Guthoff, R.,Lendlein, A. %D 2014 %J 13th European Symposium on Controlled Drug Delivery, ESCDD 2014 %N %P %T A polymeric multifunctional glaucoma implant %U %X %0 conference poster %@ %A Neffe, A.T.,Julich-Gruner, K.K.,Roch, T.,Garcia Cruz, D.M.,Naolou, T.,Brunacci, N.,Lendlein, A. %D 2014 %J Advanced Functional Polymers for Medicine, AFPM 2014 %N %P %T End group functionalized starshaped oligo(ethylene glycols) and their biological evaluation %U %X %0 conference lecture %@ %A Wischke, C.,Loebler, M.,Neffe, A.T.,Hanh, B.D.,Sternberg, K.,Stachs, O.,Guthoff, R.,Lendlein, A. %D 2014 %J Jahrestagung Deutsche Pharmazeutische Gesellschaft 2014 %N %P %T A polymeric multifunctional glaucoma implant %U %X %0 conference poster %@ %A Julich-Gruner, K.K.,Loewenberg, C.,Roch, T.,Neffe, A.T.,Lendlein, A. %D 2014 %J 6th Forum on New Materials: Symposium Smart Polymers for Biomedical Applications, CIMTEC 2014 %N %P %T Star-shaped Oligo(Ethylene Glycols) Functionalized with Desaminotyrosine and Desamino Tyrosyl Tyrosine %U %X %0 conference lecture (invited) %@ %A Lendlein, A.,Behl, M.,Neffe, A.T. %D 2014 %J 2nd International Conference on Bioinspired and Biobased Chemistry and Materials: Nature Inspires Chemical Engineers, NICE 2014 %N %P %T Design of Multifuncational Biomaterials by Chemical Integration of Functions %U %X %0 conference lecture %@ %A Gebauer, T.,Neffe, A.T.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Single Protein Adsorption to Hydrogels Obtained from Gelatin and a Diisocyanate %U %X %0 conference lecture %@ %A Racheva, M.,Julich-Gruner, K.K.,Neffe, A.T.,Wischke, C.,Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %N %P %T Functionalization Degree of Telechelics as a Structural Parameter to Influence the Properties of Enzymatically Formed Polyethylene Glycol Based Networks %U %X %0 conference lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2014 %J 2014 MRS Fall Meeting & Exhibit %N %P %T Mechanic Studies of Gelatin Crosslinking %U %X %0 lecture %@ %A Neffe, A.T.,Ober, C.K. %D 2014 %J %N %P %T Protein-Material Interactions %U %X %0 journal article %@ 2050-750X %A Neffe, A.T.,Ruesten-Lange, M.v.,Braune, S.,Luetzow, K.,Roch, T.,Richau, K.,Krueger, A.,Becherer, T.,Thuenemann, A.F.,Jung, F.,Haag, R.,Lendlein, A. %D 2014 %J Journal of Materials Chemistry B %N 23 %P 3626-3635 %R doi:10.1039/C4TB00184B %T Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility %U https://doi.org/10.1039/C4TB00184B 23 %X Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials. %0 journal article %@ 1525-7797 %A Schoenwaelder, S.M.S.,Bally, F.,Heinke, L.,Azucena, C.,Bulut, Oe.D.,Heissler, S.,Kirschhoefer, F.,Gebauer, T.P.,Neffe, A.T.,Lendlein, A.,Brenner-Weiss, G.,Lahann, J.,Welle, A.,Overhage, J.,Woell, C. %D 2014 %J Biomacromolecules %N 7 %P 2398-2406 %R doi:10.1021/bm500750v %T Interaction of Human Plasma Proteins with Thin Gelatin-Based Hydrogel Films: A QCM-D and ToF-SIMS Study %U https://doi.org/10.1021/bm500750v 7 %X In the fields of surgery and regenerative medicine, it is crucial to understand the interactions of proteins with the biomaterials used as implants. Protein adsorption directly influences cell-material interactions in vivo and, as a result, regulates, for example, cell adhesion on the surface of the implant. Therefore, the development of suitable analytical techniques together with well-defined model systems allowing for the detection, characterization, and quantification of protein adsorbates is essential. In this study, a protocol for the deposition of highly stable, thin gelatin-based films on various substrates has been developed. The hydrogel films were characterized morphologically and chemically. Due to the obtained low thickness of the hydrogel layer, this setup allowed for a quantitative study on the interaction of human proteins (albumin and fibrinogen) with the hydrogel by Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D). This technique enables the determination of adsorbant mass and changes in the shear modulus of the hydrogel layer upon adsorption of human proteins. Furthermore, Secondary Ion Mass Spectrometry and principal component analysis was applied to monitor the changed composition of the topmost adsorbate layer. This approach opens interesting perspectives for a sensitive screening of viscoelastic biomaterials that could be used for regenerative medicine. %0 journal article %@ 1042-7147 %A Neffe, A.T.,Chua, K.,Luetzow, K.,Pierce, B.F.,Lendlein, A.,Abell, A.D. %D 2014 %J Polymers for Advanced Technologies %N 11 %P 1371-1375 %R doi:10.1002/pat.3359 %T Crosslinking of gelatin by ring opening metathesis under aqueous conditions - An exploratory study %U https://doi.org/10.1002/pat.3359 11 %X Ring-opening metathesis catalysis has received little attention as a means to functionalize or crosslink biopolymers in water since the required catalysts are usually not stable under these conditions. However, biopolymer solubility suggests such a procedure. We show that Grubbs first and second generation catalysts (in emulsion) as well as a water-soluble Hoveyda-Grubbs catalyst can be applied to crosslink glycidyl methacrylated gelatin with norbornene dicarboxylic acid in water by a cross metathesis-ring opening metathesis approach. A mechanistic study suggests that cross metathesis between the functionalized polymer and the cyclic olefin acts as an initiating step for the crosslinking reaction. %0 conference lecture %@ %A Arya, N.,Gebauer, T.P.,Neffe, A.T.,Lendlein, A.,Shastri, V.P. %D 2014 %J Tissue Engineering and Regenerative Medicine International Society, Termis 2014 %N %P %T Chondrocyte re-differentiation on ethyl lysine diisocyanate cross-linked gelatin based 3-D scaffolds: Application in cartilage tissue engineering %U %X %0 conference poster %@ %A Neffe, A.T.,Ruesten-Lange, M.v.,Braune, S.,Luetzow, K.,Roch, T.,Jung, F.,Weinhart, M.,Haag, R.,Lendlein, A. %D 2014 %J Makromolekulares Kolloquium 2014 %N %P %T Polyethers on Porous Polymer Surfaces: Relevant Models to Study Protein Adsorption and Hemocompatibility %U %X %0 book part %@ %A Neffe, A.,Julich-Gruner, K.,Lendlein, A. %D 2014 %J Biomaterials for Bone Regeneration: Novel Techniques and Applications %N %P 87-109 %T Combinations of biopolymers and synthetic polymers for bone regeneration %U %X Critical bone defects do not heal by themselves, but the regeneration process can be supported by biomaterial implants. Combinations of synthetic polymers, intended to provide the required mechanical strength and processability, and biopolymers, giving cells a suitable environment for proliferation and inducing bone growth, has recently drawn attention in order to provide multifunctional implants. In this chapter, the combination of the different polymer classes on the molecular level and by surface functionalization is discussed, with an emphasis on physicochemical properties and the biological functions of the materials as well as future trends in this research field. %0 conference lecture %@ %A Neffe, A.T.,Gebauer, T.,Pierce, B.F.,Lendlein, A. %D 2013 %J 2013 MRS Spring Meeting and Exhibit %N %P %T Controlling Mechanical Properties of Biopolymer-based Materials %U %X %0 conference lecture %@ %A Rijckaert, B.,Neffe, A.T.,Roch, T.,Gebauer, T.,Pierce, B.F.,Goers, J.,Smink, J.J.,Gossen, M.,Lendlein, A.,Leutz, A. %D 2013 %J 12th International Polymers for Advanced Technologies Conference, PAT 2013 %N %P %T A High Content Screening Assay for Evaluation of Biomaterial-Mediated Cell Fusion Processes %U %X %0 lecture %@ %A Neffe, A.,Lendlein, A. %D 2013 %J %N %P %T Biopolymers; Master of Polymer Science - Advanced Topics %U %X %0 journal article %@ 0168-3659 %A Wischke, C.,Schneider, C.,Neffe, A.T.,Lendlein, A. %D 2013 %J Journal of Controlled Release %N 3 %P 321-328 %R doi:10.1016/j.jconrel.2013.02.013 %T Polyalkylcyanoacrylates as in situ formed diffusion barriers in multimaterial drug carriers %U https://doi.org/10.1016/j.jconrel.2013.02.013 3 %X Polymeric hydrogels typically release their drug payload rapidly due to their high water content and the diffusivity for drug molecules. This study proposes a multimaterial system to sustain the release by covering the hydrogel with a poly(alkyl-2-cyanoacrylate) [PACA]-based film, which should be formed by an in situ polymerization on the hydrogel surface initiated upon contact with water. A series of PACA-hydrogel hybrid systems with increasing PACA side chain hydrophobicity was prepared using physically crosslinked alginate films and hydrophilic diclofenac sodium as model hydrogel/drug system. Successful synthesis of PACA at the hydrogel surface was confirmed and the PACA layer was identified to be most homogeneous for poly(n-butyl-2-cyanoacrylate) on both the micro- and nanolevel. At the same time, the diclofenac release from the hybrid systems was substantially sustained from ~ 1 day for unmodified hydrogels up to > 14 days depending on the type of PACA employed as diffusion barrier. Overall, in situ polymerized PACA films on hydrogels may be widely applicable to various hydrogel matrices, different matrix sizes as well as more complex shaped hydrogel carriers. %0 journal article %@ 0008-6215 %A Tripodo, G.,Wischke, C.,Neffe, A.T.,Lendlein, A. %D 2013 %J Carbohydrate Research %N %P 59-63 %R doi:10.1016/j.carres.2013.08.018 %T Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers %U https://doi.org/10.1016/j.carres.2013.08.018 %X 6-O-Monotosyl-β-cyclodextrin (mono-Ts-βCD) is one of the most important intermediates in the production of substituted βCD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-βCD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10–15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-βCD was obtained with a molar purity of >98 mol %. From mono-Ts-βCD, β-cyclodextrin dimers linked by ethylenediamine (bis-Et-βCD) were successfully prepared (yield 93%, purity 96 mol %) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins. %0 journal article %@ 1946-4274 %A Julich-Gruner, K.K.,Roch, T.,Ma, N.,Neffe, A.T.,Lendlein, A. %D 2013 %J MRS Online Proceedings Library %N %P 9-14 %R doi:10.1557/opl.2013.831 %T Immunological investigations of oligoethylene glycols functionalized with desaminotyrosine and desaminotyrosyltyrosine %U https://doi.org/10.1557/opl.2013.831 %X Biomaterials require thorough in vitro testing before being applied in vivo. Unwanted contaminations of biomaterials but also their intrinsic properties can cause uncontrolled immune response leading to severe consequences for the patient. Therefore, immunological evaluation of materials for biomedical applications is mandatory before entering clinical application. In order to introduce physical netpoints, the aromatic compounds desaminotyrosine (DAT) and desaminotyrosyl-tyrosine (DATT) were successfully used to functionalize linear and star-shaped oligoethylene glycol (lOEG and sOEG) as previously described. The materials showed properties of surfactants and have potential to be used for solubilization of lipophilic drugs in water. Furthermore, the materials are susceptible for H2O2 degradation as determined by MALDI-ToF MS analyses. This is important for potential in vivo applications, as macrophages can release reactive oxygen species (ROS) under inflammatory conditions. As it is known that surfactant solutions of high concentration can lead to cell lysis, the effects of OEG-DAT(T) solutions on murine RAW macrophages were investigated. Even at highest OEG-DAT(T) concentration of 1000 µg·mL-1 the viability of the RAW cells was not significantly impaired. Additionally, the polymers were incubated with whole human blood and the production of inflammatory cytokines such as the tumor necrosis factor (TNF)-α and interleukin (IL)-6 was determined. Only at high concentrations, the OEG-DAT(T) solution induced low levels of TNF-α and IL-6, indicating that a mild inflammatory reaction could be expected when such high OEG-DAT(T) concentrations are applied in vivo. Similarly, the OEG-DAT(T) solution did not induce ROS in monocytes and neutrophils after incubation with whole human blood. Conclusively, the data presented here demonstrate that OEG-DAT(T) do not lead to a substantial activation of the innate immune mechanisms and could therefore be investigated for solubilizing pharmaceutical agents. %0 journal article %@ 1946-4274 %A Neffe, A.T.,Gebauer, T.,Lendlein, A. %D 2013 %J MRS Online Proceedings Library %N %P 3-8 %R doi:10.1557/opl.2013.837 %T Tailoring of Mechanical Properties of Diisocyanate Crosslinked Gelatin-Based Hydrogels %U https://doi.org/10.1557/opl.2013.837 %X Polymer network formation is an important tool for tailoring mechanical properties of polymeric materials. One option to synthesize a network is the addition of bivalent crosslinkers reacting with functional groups present in a polymer. In case of polymer network syntheses based on biopolymers, performing such a crosslinking reaction in water is sometimes necessary in view of the solubility of the biopolymer, such as gelatin, and can be beneficial to avoid potential contamination of the formed material with organic solvents in view of applications in biomedicine. In the case of applying diisocyanates for the crosslinking in water, it is necessary to show that the low molecular weight bifunctional crosslinker has fully reacted, while tailoring of the mechanical properties of the resulting hydrogels is possible despite the complex reaction mechanism. Here, the formation of gelatin-based hydrogel networks with the diisocyanates 2, 4-toluene diisocyanate, 1, 4-butane diisocyanate, and isophorone diisocyanate is presented. It is shown that extensive washing of materials is required to ensure full conversion of the diisocyanates. The use of different diisocyanates gives hydrogels covering a large range of Young’s moduli (12-450 kPa). The elongations at break (up to 83%) as well as the maximum tensile strengths (up to 410 kPa) of the hydrogels described here are much higher than for lysine diisocyanate ethyl ester crosslinked gelatin reported before. Rheological investigations suggest that the network formation in some cases is due to physical interactions and entanglements rather than covalent crosslink formation. %0 conference lecture %@ %A Julich-Gruner, K.K.,Roch, T.,Ma, N.,Neffe, A.T.,Lendlein, A. %D 2013 %J 2013 MRS Spring Meeting and Exhibit, Symposium MM – Advanced Materials for Biological and Biomedical Applications %N %P %T Synthesis and biological evaluation of oligoethylene glycol materials functionalized with desaminotyrosine and desaminotyrosyltyrosine %U %X %0 journal article %@ 1022-1352 %A Julich-Gruner, K.K.,Loewenberg, C.,Neffe, A.T.,Behl, M.,Lendlein, A. %D 2013 %J Macromolecular Chemistry and Physics %N 5 %P 527-536 %R doi:10.1002/macp.201200607 %T Recent Trends in the Chemistry of Shape-Memory Polymers %U https://doi.org/10.1002/macp.201200607 5 %X Shape-memory polymers (SMPs) are stimuli-sensitive materials capable of performing complex movements on demand, which makes them interesting candidates for various applications, for example, in biomedicine or aerospace. This trend article highlights current approaches in the chemistry of SMPs, such as tailored segment chemistry to integrate additional functions and novel synthetic routes toward permanent and temporary netpoints. Multiphase polymer networks and multimaterial systems illustrate that SMPs can be constructed as a modular system of different building blocks and netpoints. Future developments are aiming at multifunctional and multistimuli-sensitive SMPs. %0 journal article %@ 1946-4274 %A Gebauer, T.,Neffe, A.T.,Lendlein, A. %D 2013 %J MRS Online Proceedings Library %N %P 15-20 %R doi:10.1557/opl.2013.839 %T Influence of diisocyanate reactivity and water solubility on the formation and the mechanical properties of gelatin-based networks in water %U https://doi.org/10.1557/opl.2013.839 %X Gelatin can be covalently crosslinked in aqueous solution by application of diisocyanates like L-lysine diisocyanate ethyl ester in order to form hydrogels. Reaction of isocyanate groups with water is however a limiting factor in hydrogel network formation and can strongly influence the outcome of the crosslinking process. Here, diisocyanates with different water solubility and reactivity were applied for the formation of gelatin-based hydrogel networks and the mechanical properties of the hydrogels were investigated to gain a better understanding of starting material/ hydrogel property relations. L-Lysin diisocyanate ethyl ester (LDI), 2, 4-toluene diisocyanate (TDI), 1, 4-butane diisocyanate (BDI), and isophorone diisocyanate (IPDI) were selected, having different solubility in water ranging from 10-4 to 10-2 mol·L-1. BDI and LDI were estimated to have average reactive isocyanates groups, whereas TDI is highly reactive and IPDI has low reactivity. Formed hydrogels showed different morphologies and were partially very inhomogeneous. Gelation time (1 to 50 minutes), water uptake (300 to 900 wt.-%), and mechanical properties determined by tensile tests (E-moduli 35 to 370 kPa) and rheology (Shear moduli 4.5 to 19.5 kPa) showed that high water solubility as well as high reactivity leads to the formation of poorly crosslinked or inhomogeneous materials. Nevertheless, diisocyanates with lower solubility in water and low reactivity are able to form stable, homogeneous hydrogel networks with gelatin in water. %0 editorial %@ 1616-5187 %A Lendlein, A.,Neffe, A.T. %D 2013 %J Macromolecular Bioscience %N 12 %P 1639-1639 %R doi:10.1002/mabi.201300507 %T Advanced Functional Polymers for Medicine %U https://doi.org/10.1002/mabi.201300507 12 %X The application of polymers in medicine requires tailored properties and functions. While properties are material inherent (e.g. thermal transitions, mechanical properties), functions can only be realized by combining a certain molecular structure with physical principles, such as the shape-memory effect based on entropy elasticity of a network and suitable phase transitions, while drug release is ruled by diffusion and interactions at interfaces. %0 editorial %@ 1022-1360 %A Lendlein, A.,Neffe, A.T. %D 2013 %J Macromolecular Symposia %N 1 %P 8-9 %R doi:10.1002/masy.201370041 %T Preface: Advanced Functional Polymers in Medicine %U https://doi.org/10.1002/masy.201370041 1 %X This volume of Macromolecular Symposia is the conference proceeding volume from the 533th WE-Heraeus Seminar “Advanced Functional Polymers for Medicine” held in Bad Honnef, Germany, from May 27 to May 29, 2013. The meeting was organized by Andreas Lendlein and Axel T. Neffe as the third conference in the annual Advanced Functional Polymers for Medicine conference series %0 journal article %@ 1616-5187 %A Neffe, A.T.,Von Ruesten-Lange, M.,Braune, S.,Luetzow, K.,Roch, T.,Richau, K.,Jung, F.,Lendlein, A. %D 2013 %J Macromolecular Bioscience %N 12 %P 1720-1729 %R doi:10.1002/mabi.201300309 %T Poly(ethylene glycol) Grafting to Poly(ether imide) Membranes: Influence on Protein Adsorption and Thrombocyte Adhesion %U https://doi.org/10.1002/mabi.201300309 12 %X The chain length and end groups of linear PEG grafted on smooth surfaces is known to influence protein adsorption and thrombocyte adhesion. Here, it is explored whether established structure function relationships can be transferred to application relevant, rough surfaces. Functionalization of poly(ether imide) (PEI) membranes by grafting with monoamino PEG of different chain lengths (Mn = 1 kDa or 10 kDa) and end groups (methoxy or hydroxyl) is proven by spectroscopy, changes of surface hydrophilicity, and surface shielding effects. The surface functionalization does lead to reduction of adsorption of BSA, but not of fibrinogen. The thrombocyte adhesion is increased compared to untreated PEI surfaces. Conclusively, rough instead of smooth polymer or gold surfaces should be investigated as relevant models. %0 journal article %@ 0168-3659 %A Wischke, C.,Neffe, A.T.,Hanh, B.D.,Kreiner, C.F.,Sternberg, K.,Stachs, O.,Guthoff, R.F.,Lendlein, A. %D 2013 %J Journal of Controlled Release %N 3 %P 1002-1010 %R doi:10.1016/j.jconrel.2013.10.021 %T A multifunctional bilayered microstent as glaucoma drainage device %U https://doi.org/10.1016/j.jconrel.2013.10.021 3 %X Commercial non-degradable glaucoma implants are often associated with undesired hypotony, fibrosis, long term failure, and damage of adjacent tissues, which may be overcome by a multifunctional polymeric microstent for suprachoroidal drainage. This study reports the design and fabrication of such devices with tailorable internal diameters (50–300 μm) by solvent-free, continuous hot melt extrusion from blends of poly[(ε-caprolactone)-co-glycolide] and poly(ε-caprolactone) [PCL]. A spatially directed release was supported by bilayered microstents with an internal drug-free PCL layer, and a quantitative description of release kinetics with diclofenac sodium as model drug was provided. Furthermore, the slow degradation pattern (> 1 year) was analyzed and potential effects of 1–5 wt.% drug loading on material properties were excluded. Translational aspects including sterilization by γ-irradiation on dry ice, in vitro biocompatibility, and in vivo implantation were addressed. The promising results support further functional analysis of long-term in vivo performance and suppression of disadvantageous capsule formation. %0 journal article %@ 1743-4440 %A Neffe, A.T.,Wischke, C.,Racheva, M.,Lendlein, A. %D 2013 %J Expert Review of Medical Devices %N 6 %P 813-833 %R doi:10.1586/17434440.2013.839209 %T Progress in biopolymer-based biomaterials and their application in controlled drug delivery %U https://doi.org/10.1586/17434440.2013.839209 6 %X Biopolymer-based materials are based on re-growing resources and are attractive for biomedical applications, as they can inherently combine degradability in vivo, can offer sites of adhesion for cells and proteins, often show good biocompatibility and may additionally be used to release embedded bioactive molecules. However, their selection and efficient use for specific applications require an understanding of molecular principles and relationships between the molecular and macroscopic level to establish distinct properties and functions. Here, synthetic routes are described, which allow tailoring properties and functions of biopolymer-based materials. The biological evaluation of such materials is discussed, with a special emphasis on their application in controlled release systems such as hydrogels and particulate carriers. %0 conference lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2013 %J Eroeffnung der Graduiertenschule MacroBio %N %P %T Biopolymer-based Biomaterials %U %X %0 conference lecture (invited) %@ %A Neffe, A.T.,Gebauer, T.,Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %N %P %T Tailoring the elastic properties and protein adsorption of gelatin-based networks by crosslinking with diisocyanates of differing reactivity and solubility in water %U %X %0 journal article %@ 0168-3659 %A Wischke, C.,Schneider, C.,Neffe, A.T.,Lendlein, A. %D 2013 %J Journal of Controlled Release %N 1 %P e 22 %R doi:10.1016/j.jconrel.2013.08.052 %T Sustained release hydrogels by in situ polymerized polyalkylcyanoacrylate coating %U https://doi.org/10.1016/j.jconrel.2013.08.052 1 %X No abstract %0 journal article %@ 1022-1360 %A Racheva, M.,Julich-Gruner, K.K.,Nöchel, U.,Neffe, A.T.,Wischke, C.,Lendlein, A. %D 2013 %J Macromolecular Symposia %N 1 %P 24-32 %R doi:10.1002/masy.201300112 %T Influence of Drying Procedures on Network Formation and Properties of Hydrogels from Functionalized Gelatin %U https://doi.org/10.1002/masy.201300112 1 %X Side chain functionalization of gelatin with tyrosine-derived moieties, desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT), has been reported to lead to physical networks stabilized by aromatic interactions and hydrogen bonds, while the inherent ability of gelatin chains to organize in helices is suppressed. Here, the treatment of DAT and DATT gelatin films at defined temperatures (drying at 5 °C, freeze-drying, and freeze-thawing) were explored for the potential to additionally stabilize the hydrogels by increasing the content of helical domains as additional physical netpoints. The influence of the drying procedures on the hydrogel properties such as network morphology and mechanical properties were analyzed by WAXS, swelling, and rheological measurements. The triple helix content had a stabilizing effect on gelatin-based hydrogels at temperatures below the helix-to-coil transition. However, this effect was less pronounced at physiological conditions above the transition temperature, resulting in rapid dissolution of the physical gelatin networks. %0 conference poster %@ %A Luetzow, K.,Weigel, T.,Kosmella, H.-J.,Neffe, A.T.,Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %N %P %T Shape-Memory Effect of Polymeric Nanocomposite Polyether Urethane Foams with Magnetic Nanoparticles %U %X %0 conference poster %@ %A Julich-Gruner, K.,Roch, T.,Neffe, A.T.,Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %N %P %T Functionalization of Polymers with the Amino Acid derived Moieties Desaminotyrosine and Desaminotyrosyl Tyrosine %U %X %0 conference poster %@ %A Rijckaert, B.,Pierce, B.F.,Neffe, A.T.,Goers, J.,Roch, T.,Gebauer, T.,Smink, J.J.,Lendlein, A.,Gossen, M.,Leutz, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %N %P %T Evaluation of Gelatin Hydrogels in their Interaction with Monocytic Osteoclast Precursor Cells %U %X %0 conference poster %@ %A Gebauer, T.,Neffe, A.T.,Lendlein, A. %D 2013 %J 2013 MRS Spring Meeting and Exhibit, Symposium MM – Advanced Materials for Biological and Biomedical Applications %N %P %T Influence of diisocyanate reactivity and water solubility on the formation of gelatin-based networks in water %U %X %0 conference poster %@ %A Ullm, S.,Tondera, C.,Gebauer, T.,Neffe, A.T.,Lendlein, A.,Pietzsch, J. %D 2013 %J World Conference on Regenerative Medicine, WCRM 2013 %N %P %T Gelatin-based biomaterials with tailorable mechanical properties as promising matrices for soft tissue replacement %U %X %0 conference lecture %@ %A Gebauer, T.,Neffe, A.T.,Lendlein, A. %D 2013 %J HVI Method Workshop 2013 %N %P %T Protein Adsorption to Gelatin-based Biomaterials %U %X %0 conference lecture %@ %A Santan, H.,Wischke, C.,Neffe, A.,Lendlein, A. %D 2013 %J HVI Method Workshop 2013 %N %P %T Protein Adsorption to Synthetic Polymers %U %X %0 journal article %@ 1386-0291 %A Krueger, A.,Goers, J.,Zaupa, A.,Loewenberg, C.,Pierce, B.F.,Wischke, C.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1 %P 133-142 %R doi:10.3233/CH-131697 %T Influence of physically crosslinked gelatins on the vasculature in the avian chorioallantoic membrane %U https://doi.org/10.3233/CH-131697 1 %X Gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) form physically crosslinked hydrogels, due to the interactions between the introduced aromatic moieties and gelatin triple helices, whose extent depends on the thermal treatment of the material. The G-modulus of these hydrogels can be tailored to the range of the natural extracellular matrix by adjusting the degree of crosslinking. While these gelatin-based materials have been shown to be not angiogenic, the aim of the study was to evaluate whether these biomaterials influence the regulation of blood vessels when positioned on the chorionallantoic membrane (CAM) of fertilized eggs. The results clearly indicate that the DAT-functionalized gelatin led to an increase of the diameter of the blood vessels in the CAM, which at the same time is probably associated with an increased blood flow in these CAM vessels. The vessel diameters of the four groups (DAT-functionalized gelatin, DATT-functionalized gelatin, plain gelatin, control group without gelatin, each n = 10) differed significantly (p < 0.0001). Vessels in the CAM exposed to the DAT-functionalized gelatin showed with 36.4 μm ± 3.4 μm the largest mean diameters compared to the mean diameters of the samples exposed to DATT gelatin (16.0 μm ± 0.8 μm; p < 0.05) and the plain gelatin (21.2 μm ± 1.0 μm; p < 0.05), which both did not differ significantly from the vessels of the control group. The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (one hour up to several days). %0 journal article %@ 1386-0291 %A Braune, S.,Ruesten-Lange, M.v.,Mrowietz, C.,Luetzow, K.,Roch, T.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 3 %P 235-248 %R doi:10.3233/CH-131729 %T Dynamic in vitro hemocompatibility testing of poly(ether imide) membranes functionalized with linear, methylated oligoglycerol and oligo(ethylene glycol) %U https://doi.org/10.3233/CH-131729 3 %X Linear, side-chain methylated oligoglycerols (OGMe) were recently reported as potential surface passivating molecules for improving the protein resistance of cardiovascular application relevant poly(ether imide) (PEI) membranes. A previously reported in vitro screening under static test conditions allowed an end-point evaluation of the adhesion and activation of adherent thrombocytes performed on the material surfaces and revealed similar levels of thrombogenicity on PEI membranes, functionalized with OGMe and oligo(ethylene glycol) (OEG) of similar molecular weight (Mn = 1,300 g·mol−1 - 1,800 g·mol−1). In the present study, we investigated the hemocompatibility of these materials in a dynamic closed loop system, in order to study time-dependent thrombocyte material interactions also of the circulating thrombocytes by mimicking in vivo relevant flow conditions in a dynamic test system with multiple material contacts. Activation and aggregation of circulating thrombocytes as well as complement activation and plasmatic coagulation were evaluated after 40 circulations of thrombocyte rich plasma in the closed loop system. The results of the dynamic tests revealed no differences between the OGMe and OEG functionalized PEI membranes. Furthermore, no differences were observed between the latter and a PEI membrane treated under the conditions of functionalization at pH 11 (PEI-pH11) without an oligoether being present. Blood plasma protein adsorption, as well as activation, and adherence of circulating thrombocytes occurred in a comparable, but minor manner on all investigated PEI membranes. From this we conclude that the OGMe and OEG surface functionalization did not lead to an improvement of the already good hemocompatibility of the PEI-pH11 membrane. %0 conference lecture %@ %A Wischke, C.,Neffe, A.T.,Ruesten-Lange, M.v.,Braune, S.,Luetzow, K.,Roch, T.,Richau, K.,Jung, F.,Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %N %P %T The Suitability of Polyethers to Reduce Protein Adsorption and to Improve Hemocompatibility %U %X %0 conference poster %@ %A Gebauer, T.,Neffe, A.T.,Lendlein, A. %D 2013 %J 28. Tag der Chemie %N %P %T Influence of diisocyanate reactivity and water solubility on the formation of gelatin-based networks in water %U %X %0 conference lecture %@ %A Ma, N.,Luetzow, C.,Kratz, K.,Furlani, D.,Li, W.,Wang, W.,Pittermann, E.,Neffe, A.T.,Sauter, T.,Jung, F.,Lendlein, A. %D 2013 %J 17th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2013 %N %P %T A three-dimensional stem cell culture system by polyurethane scaffold material %U %X %0 conference poster %@ %A Racheva, M.,Julich-Gruner, K.,Noechel, U.,Neffe, A.T.,Wischke, C.,Lendlein, A. %D 2013 %J Advanced Functional Polymers for Medicine, 533th WE-Heraeus-Seminar %N %P %T Influence of drying procedures on network properties of physical gelatin hydrogels %U %X %0 journal article %@ %A Neffe, A.T.,Scharnagl, N.,Behl, M.,Lendlein, A. %D 2012 %J BioTOPics : Journal of Biotechnology in Berlin-Brandenburg %N %P 8-10 %T Biomaterials in Regenerative Medicine %U %X Regenerative Therapies require biomaterials with properties and functions tailored to the tion' demands of a specific applica- Especially in biomaterial induced auto-regeneration, multifunctional polymer-based biomaterials are of high rel- evance' The cooperation of scientists from different disciplines is essential in order to perform research and development,of biomaterials directed to clinical applications and products. Here, fundamental research for polymer based biomaterials,meets application-motivated science aiming at translation of the gained knowledge into products and clinical applications. %0 conference lecture (invited) %@ %A Neffe, A.T.,Lendlein, A. %D 2012 %J Improving Health for the Ageing Society, Dialogue Forum %N %P %T Biomaterials for Regenerative Medicine %U %X %0 conference poster %@ %A Julich-Gruner, K.K.,Neffe, A.T.,Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %N %P %T Synthesis and characterization of oligo(ethylene glycol)s functionalized with desaminotyrosine or desaminotyrosyltyrosine %U %X %0 conference poster %@ %A Goers, J.,Mayer, A.,Zaupa, A.,Pierce, B.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Influence of physically (DAT) crosslinked gelatin on the vasculature in the avian chorioallantoic membrane %U %X %0 conference lecture %@ %A Goers, J.,Krueger, A.,Gebauer, T.,Pierce, B.F.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2012 %J 14th International Congress of Biorheology, 7th International Conference on Clinical Hemorheology %N %P %T Influence of chemically crosslinked gelatin on the vasculature in the avian chorioallantoic membrane %U %X %0 journal article %@ 1616-5187 %A Pierce, B.F.,Pittermann, E.,Ma, N.,Gebauer, T.,Neffe, A.T.,Hoelscher, M.,Jung, F.,Lendlein, A. %D 2012 %J Macromolecular Bioscience %N 3 %P 312-321 %R doi:10.1002/mabi.201100237 %T Viability of Human Mesenchymal Stem Cells Seeded on Crosslinked Entropy-Elastic Gelatin-Based Hydrogels %U https://doi.org/10.1002/mabi.201100237 3 %X Biomimetic polymer network systems with tailorable properties based on biopolymers represent a class of degradable hydrogels that provides sequences for protein adsorption and cell adhesion. Such materials show potential for in vitro MSC proliferation as well as in vivo applications and were obtained by crosslinking different concentrations of gelatin using varying amounts of ethyl lysine diisocyanate in the presence of a surfactant in pH 7.4 PBS solution. Material extracts, which were tested for cytotoxic effects using L929 mouse fibroblasts, were non-toxic. The hydrogels were seeded with human bone marrow-derived MSCs and supported viable MSCs for the incubation time of 9 d. Preadsorption of fibronectin on materials improved this biofunctionality. %0 journal article %@ 1946-4274 %A Piece, B.F.,Neffe, A.T.,Lendlein, A. %D 2012 %J MRS Online Proceedings Library %N %P 13-18 %R doi:10.1557/opl.2012.221 %T Using Mass Spectrometry to Investigate the Structural Features of Photocrosslinked Co-Networks based on Gelatin and Poly(ethylene glycol) Methacrylates %U https://doi.org/10.1557/opl.2012.221 %X Gelatin was functionalized with glycidyl methacrylate and photocrosslinked in the presence of poly(ethylene glycol) dimethacrylate (PEGDMA) or poly(ethylene glycol) monomethacrylate (PEGMA) to create a biopolymer-based system with tailorable properties. These co-networks were hydrolyzed using 6 M HCl and the degradation products were analyzed and identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. This technique successfully identified gelatin-derived peptides such as FLPEPPE, SFLPEPPE, and SFLPEPPEE as well as an accompanying PEG-g-poly(methacrylic acid) component. No oligo- or polymethacrylates were monitored at any molecular weight range above m/z = 500, which indicated that they possessed lower molecular weights. An in vitro hydrolytic degradation experiment performed in pH 7.4 PBS buffer solution at 37 °C showed that these networks, which were prepared without the addition of a potentially toxic photoinitiator, exhibited mass loss of up to 50 wt% at 6 weeks of incubation time. These results provide valuable insight into how these functional gelatin-based co-network biomaterials will perform in a biological setting. %0 journal article %@ 1616-5187 %A Pierce, B.F.,Tronci, G.,Roessle, M.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2012 %J Macromolecular Bioscience %N 4 %P 484-493 %R doi:10.1002/mabi.201100232 %T Photocrosslinked Co-Networks from Glycidylmethacrylated Gelatin and Poly(ethylene glycol) Methacrylates %U https://doi.org/10.1002/mabi.201100232 4 %X Biopolymer-based systems with adjustable macroscopic properties that can be varied in a wide range using only small changes in chemical composition are promising candidates for biomaterial-induced autoregeneration. Glycidylmethacrylated gelatin is photopolymerized with the addition of PEG mono- or dimethacrylate to form co-networks in pH = 7.4 PBS. The degree of swelling (Q) and water uptake (H) in PBS at 37 °C are tailorable for PEGDMA co-networks (Q ≈ 250–650 vol%), while the storage modulus of swollen networks at 37 °C can be adjusted by the PEG(D)MA content (G′ = 0.7–145 kPa). Indirect cytotoxicity tests on ethylene oxide sterilized films show non-toxic responses for the homonetwork and all but one PEGDMA-containing co-networks materials. %0 conference poster %@ %A Julich-Gruner, K.K.,Neffe, A.T.,Lendlein, A. %D 2012 %J Polydays 2012 %N %P %T Synthesis and characterization of oligo(ethylene glycol)s functionalized with desaminotyrosine or desaminotyrosyltyrosine %U %X %0 journal article %@ %A Neffe, A.T.,Lendlein, A. %D 2012 %J Berliner Wirtschaftsgespraeche, Themenbroschuere 2012, Gesundheitsstandort Berlin und Brandenburg %N %P 73-74 %T Biomaterialien: Ein Gewinn fuer die Regenerative Medizin und den Gesundheitsstandort Berlin-Brandenburg %U %X Biomaterialien sind Bestandteil regenerativer Therapien. Durch Vernetzung von herausragender Grundlagenforschung, klinischer Forschung mit Anwendungsorientierter Forschung und Entwicklung sowie einer interdisziplinären Ausbildung wird die gesamte Entwicklungskaskade abgebildet, so dass die Biomaterialforschung in der Region Berlin-Brandenburg einen internationalen Spitzenplatz belegt. %0 conference poster %@ %A Wischke, C.,Schneider, C.,Neffe, A.T.,Lendlein, A. %D 2012 %J 2nd Symposium on Innovative Polymers for Controlled Delivery, SIPCD 2012 %N %P %T Sustained release hydrogels by in situ polymerized coating with polyalkylcyanoacrylates %U %X %0 conference lecture (invited) %@ %A Neffe, A.T.,Pierce, B.F.,Jung, F.,Ma, N.,Lendlein, A. %D 2012 %J Chemistry Seminar Flinders University %N %P %T Biomimetic Polymers for Biomedical Applications %U %X %0 journal article %@ 2280-8000 %A Julich-Gruner, K.K.,Neffe, A.T.,Lendlein, A. %D 2012 %J Journal of Applied Biomaterials & Functional Materials %N 3 %P 170-176 %R doi:10.5301/JABFM.2012.10342 %T Synthesis and characterization of oligo(ethylene glycol)s functionalized with desaminotyrosine or desaminotyrosyltyrosine %U https://doi.org/10.5301/JABFM.2012.10342 3 %X Purpose: The aromatic compounds desaminotyrosine (DAT) and desaminotyrosyltyrosine (DATT) have been successfully used to functionalize gelatin in order to form physically crosslinked networks via π-π interactions and hydrogen bonds of the introduced phenol moieties. Here, it was explored whether this concept can be applied to a synthetic polymer not engaging in additional interactions such as triple helix formation in gelatin, enabling a network to form by physical interactions mainly related to the terminal functional groups. Oligo(ethylene glycol) (OEG) was chosen as hydrophilic synthetic polymer for the backbone structure. Methods: Linear OEG (MP = 3 kDa) and four-arm OEG (Mn = 5 kDa) with amino functionalities as endgroups were functionalized with DAT and DATT using EDC·HCl and NHS as activating agents. The compounds were characterized by NMR, IR spectroscopy, and MALDI. Rheological behavior of aqueous solutions of the polymers was studied. The critical micelle concentration (CMC) was determined by a fluorescence spectroscopic analysis using the hydrophobic fluorescent dye pyrene. Results: DATT-functionalized linear OEG, four-arm DAT-functionalized OEG and four-arm DATT-functionalized OEG were synthesized with degrees of functionalization of 60-95 mol%. All compounds were water soluble, and rheological measurements revealed a decrease in storage modulus G’ and loss modulus G’’ compared to unfunctionalized OEG. Moreover, the CMC of linear OEG-DATT could be determined. Conclusions: The syntheses of OEG functionalized with the aromatic compounds DAT and DATT was reported. The polymers showed the properties of a surfactant. %0 conference lecture %@ %A Neffe, A.T.,Pierce, B.F.,Lendlein, A. %D 2012 %J 39th Congress of the European Society for Artificial Organs, ESAO 2012 %N %P %T Control of Mechanical Properties in Biopolymer-Based Biomaterials %U %X %0 conference paper %@ %A Piece, B.F.,Neffe, A.T.,Lendlein, A. %D 2012 %J MRS Symposium Proceedings, Multifunctional Polymer-Based Materials, 2011 MRS Fall Meeting %N %P 159-165 %T Using Mass Spectrometry to Investigate the Structural Features of Photocrosslinked Co-Networks based on Gelatin and Poly(ethylene glycol) Methacrylates %U %X %0 conference paper %@ %A Neffe, A.T.,Pierce, B.F.,Blaszkiewicz, J.,Lendlein, A. %D 2012 %J MRS Symposium Proceedings, Multifunctional Polymer-Based Materials, 2011 MRS Fall Meeting %N %P 145-150 %T Quantifying Protein Adsorption to Physically Crosslinked Gelatin-Based Networks %U %X %0 conference lecture (invited) %@ %A Neffe, A.T.,Pierce, B.F.,Jung, F.,Ma, N.,Lendlein, A. %D 2012 %J Chemistry Seminar University of Adelaide %N %P %T Biomimetic Polymers for Biomedical Applications %U %X %0 conference lecture (invited) %@ %A Lendlein, A.,Pierce, B.F.,Neffe, A.T. %D 2012 %J 9th World Biomaterials Congress %N %P %T Knowledge-based design of degradable polymers %U %X %0 journal article %@ 2280-8000 %A Lange, M.,Luetzow, K.,Neffe, A.T.,Lendlein, A. %D 2012 %J Journal of Applied Biomaterials & Functional Materials %N 3 %P 215-222 %R doi:10.5301/JABFM.2012.10345 %T Characterization of Oligo(ethylene glycol) and Oligoglycerol functionalized Poly(ether imide) by Angle-dependent X-ray Photoelectron Spectroscopy %U https://doi.org/10.5301/JABFM.2012.10345 3 %X Purpose: Previous investigations have shown that poly(ether imide) (PEI) membranes can be functionalized with aminated macromolecules. In this study we explored whether the characterization of PEI functionalized with oligo(ethylene glycol) (OEG) or linear, side chain methylated oligoglycerols (OGMe), by angle-dependent X-ray induced photoelectron spectroscopy (XPS) can be used to prove the functionalization, give insight into the reaction mechanism and reveal the spatial distribution of the grafts. 
Methods: PEI membranes were functionalized under alkaline conditions using an aqueous solution with 2 wt% of α-amino-ω-methoxy oligo(ethylene glycol) (Mn = 1,320 g·mol-1) or linear, side chain methylated monoamine oligoglycerols (Mn = 1,120, 1,800 or 2,270 g·mol-1), respectively. The functionalized membranes were investigated using XPS measurements at different detector angles to enable comparison between the signals related to the bulk and surface volume and were compared with untreated and alkaline-treated PEI membranes.
 Results: While at a perpendicular detector angle the bulk signals of the PEI were prominent, at larger surface volume-related detector angles, the signals for OGMe and OEG were determinable. 
Conclusion: The surface functionalization of PEI with OEG and OGMe could be verified by the angle-dependent XPS. The observations proved the functionalization at the PEI surface, as the polyethers were detected at angles providing signals of the surface volume. Furthermore, the chemical functions determined verified a covalent binding via the nucleophilic addition of the amine functionalized OGMe and OEG to the PEI imide function. %0 conference lecture %@ %A Lange, M.,Luetzow, K.,Neffe, A.T.,Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %N %P %T Characterization of Oligo(ethylene glycol) and Oligoglycerol functionalized Poly(ether imide) by Angle-dependent X-ray Photoelectron Spectroscopy %U %X %0 conference poster %@ %A Neffe, A.T.,Santan, H.D.,Kamlage, S.,Lendlein, A. %D 2012 %J GDCh Biannual Meeting of the GDCh-Division Macromolecular Chemistry, Smart Polymers %N %P %T Thermal Gelation and Stability of Pectin and Chondroitin Sulfate Grafted with Poly(ethylene glycol-b-propylene glycol-b-ethylene glycol) %U %X %0 conference poster %@ %A Neffe, A.T.,Zaupa, A.,Pierce, B.F.,Roch, T.,Jung, F.,Lendlein, A. %D 2012 %J COST Namabio 2nd Joint Meeting %N %P %T Functionalization of Gelatin with Tyrosine Moieties: A Supramolecular Approach to Biomaterials %U %X %0 conference paper %@ %A Santan, H.D.,Neffe, A.T.,Kamlage, S.,Lendlein, A. %D 2012 %J MRS Symposium Proceedings, Multifunctional Polymer-Based Materials, 2011 MRS Fall Meeting %N %P 151-158 %T Thermal Gelation and Stability of Pectin Grafted with PEPE %U %X %0 journal article %@ 1022-1336 %A Lange, M.,Braune, S.,Luetzow, K.,Richau, K.,Scharnagl, N.,Weinhart, M.,Neffe, A.T.,Jung, F.,Haag, R.,Lendlein, A. %D 2012 %J Macromolecular Rapid Communications %N 17 %P 1487-1492 %R doi:10.1002/marc.201200426 %T Surface Functionalization of Poly(ether imide) Membranes with Linear, Methylated Oligoglycerols for Reducing Thrombogenicity %U https://doi.org/10.1002/marc.201200426 17 %X Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers. %0 journal article %@ 1386-0291 %A Jung, F.,Goers, J.,Roch, T.,Zaupa, A.,Pierce, B.,Neffe, A.T.,Lendlein, A. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 55-63 %R doi:10.3233/CH-2011-1443 %T Physically crosslinked gelatins functionalized with tyrosine moieties do not induce angiogenesis or thrombus formation in the developing vasculature in the avian chorioallantoic membrane %U https://doi.org/10.3233/CH-2011-1443 1-2 %X Gelatins functionalized with desaminotyrosine or desaminotyrosyl tyrosine form physically crosslinked polymer networks due to the interactions between the introduced aromatic moeties. In the swollen state, their mechanical properties can be tailored in a range similar to the elasticity of soft tissues. The aim of this study was to evaluate their potential as biomaterials by determining whether these materials – in comparison to plain gelatin – induce bleedings, thrombotic processes, or angiogenesis. These investigations were performed using the hen's egg chorioallantoic membrane (HETCAM) assay. These results indicate that the gelatin-based hydrogels did not possess angiogenic effects and also did not induce bleedings, thrombotic processes or vessel destruction (avascular zones). The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (1 hour up to several days). %0 conference lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2012 %J TERM - Trends and challenges in Regenerative Medicine - Towards interregional collaboration in Europe %N %P %T Biomaterials for Regenerative Medicine %U %X %0 conference lecture (invited) %@ %A Neffe, A.T.,Lendlein, A. %D 2012 %J Medi-WING, Medizintechnik im BMBF-Foerderprogramm WING %N %P %T Zukunftsperspektiven in der Biomaterialforschung %U %X %0 conference poster %@ %A Neffe, A.T.,Lange, M.,Braune, S.,Luetzow, K.,Jung, F.,Scharnagl, N.,Richau, K.,Weinhart, M.,Haag, R.,Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %N %P %T Surface Functionalization of Poly(ether imide) with Linear, Methylated Oligoglycerols to Increase the Hemocompatibility %U %X %0 conference lecture (invited) %@ %A Neffe, A.T.,Behl, M.,Jung, F.,Pierce, B.F.,Lendlein, A. %D 2012 %J Smart Collaborations Seminar %N %P %T Biopolymer-Based Materials for Medical Applications %U %X %0 journal article %@ 0391-3988 %A Lendlein, A.,Neffe, A.T.,Pierce, B.,Vienken, J. %D 2011 %J The International Journal of Artificial Organs %N 2 %P 71-75 %R doi:10.5301/IJAO.2011.6422 %T Why are so few degradable polymeric biomaterials currently established in clinical applications? %U https://doi.org/10.5301/IJAO.2011.6422 2 %X No abstract %0 conference poster %@ %A Tripodo, G.,Wischke, C.,Neffe, A.T.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Highly elastic poly(ethyl-2-cyanoacrylate) based materials obtained by incorporation of oligo(ethylene glycol) diglycidyl ether as a softener %U %X %0 conference poster %@ %A Roch, T.,Pierce, B.F.,Zaupa, A.,Goers, J.,Jung, F.,Neffe, A.T.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Analysis of Endotoxin Content and Evaluation of Angiogenic Effects of Desaminotyrosine- and Desaminotyrosyl Tyrosine-Functionalized Gelatin %U %X %0 journal article %@ 1742-7061 %A Neffe, A.T.,Loebus, A.,Zaupa, A.,Stoetzel, C.,Mueller, F.A.,Lendlein, A. %D 2011 %J Acta Biomaterialia %N 4 %P 1693-1701 %R doi:10.1016/j.actbio.2010.11.025 %T Gelatin Functionalization with Tyrosine Derived Moieties for Increasing the Interaction with Hydroxyapatite Fillers %U https://doi.org/10.1016/j.actbio.2010.11.025 4 %X Combining gelatins functionalized with the tyrosine-derived groups desaminotyrosine or desaminotyrosyl tyrosine with hydroxyapatite (HAp) led to the formation of composite materials with much lower swelling ratio than of the pure matrices. Shifts of IR bands related to the free carboxyl groups could be observed in the presence of HAp, which suggested a direct interaction of matrix and filler that formed additional physical crosslinks in the material. In tensile tests and rheological measurements, the composites equilibrated in water had increased Young’s moduli (from 200 kPa up to 2 MPa) and tensile strength (from 57 kPa up to 1.1 MPa) compared to the matrix polymers without affecting the elongation at break. Furthermore, an increased thermal stability from 40 °C to 85 °C of the networks could be demonstrated. The differences of the behaviour of the functionalized gelatins to pure gelatin as matrix suggested an additional stabilizing bond between the incorporated aromatic groups to the hydroxyapatite as supported by the IR results. The composites can potentially be applied as bone fillers. %0 conference poster %@ %A Kobuch, K.A.,Maier, M.,Feucht, N.,Wolfstein, A.,Streufert, D.,Lohmann, C.P.,Kamlage, S.,Neffe, A.T.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T In vivo Evaluation of a Multifunctional Hydrogel System for Local Application on the Retina %U %X %0 conference poster %@ %A Neffe, A.T.,Kobuch, K.A.,Maier, M.,Feucht, N.,Lohmann, C.P.,Wolfstein, A.,Streufert, D.,Kamlage, S.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T In vitro and in vivo Evaluation of a Multifunctional Hyaluronic acid based Hydrogel System for Local Application on the Retina %U %X %0 journal article %@ 1552-4973 %A Loebler, M.,Sternberg, K.,Stachs, O.,Allemann, R.,Grabow, N.,Roock, A.,Kreiner, C.F.,Streufert, D.,Neffe, A.T.,Hanh, B.D.,Lendlein, A.,Schmitz, K.-P.,Guthoff, R. %D 2011 %J Journal of Biomedical Materials Research B %N 2 %P 388-395 %R doi:10.1002/jbm.b.31826 %T Polymers and drugs suitable for the development of a drug delivery drainage system in glaucoma surgery %U https://doi.org/10.1002/jbm.b.31826 2 %X Implantation of a glaucoma drainage system is an appropriate therapeutic intervention in some glaucoma patients. However, one drawback with this approach is the fibrotic tissue response to the implant material, leading to reduced flow of aqueous liquid or complete blockage of the drainage system. As a basis for developing an aqueous shunt we report here investigations with poly(3-hydroxybutyrate) (P(3HB)) and poly(4-hydroxybutyrate) (P(4HB)) as polymer matrices and with paclitaxel (PTX) and triamcinolone acetonide (TA) as drugs that might, in combination, delay or prevent the process of fibrosis by reducing fibroblast activity. P(3HB) and P(4HB) were fabricated into test prototypes with 500 μm outer and 200 μm inner diameter and ∼1 cm length. The antiproliferative agent PTX and the anti-inflammatory agent TA were incorporated into the polymer matrices and were released by diffusion. In vitro cell assays demonstrated that the polymers have the potential to reduce fibroblast viability, while TA showed differential inhibition of Tenon fibroblasts, but not cornea keratocytes. Implantation of polymer disks and prototype devices into rabbit eyes confirmed the good biocompatibility of the materials. The combined use of a poly(hydroxybutyrate) polymer with PTX or TA has the potential to reduce the fibrosis associated with conventional glaucoma drainage systems. %0 journal article %@ 1525-7797 %A Zaupa, A.,Neffe, A.T.,Pierce, B.F.,Noechel, U.,Lendlein, A. %D 2011 %J Biomacromolecules %N 1 %P 75-81 %R doi:10.1021/bm101029k %T Influence of Tyrosine-Derived Moieties and Drying Conditions on the Formation of Helices in Gelatin %U https://doi.org/10.1021/bm101029k 1 %X The single and triple helical organization of protein chains strongly influences the mechanical properties of gelatin-based materials. A chemical method for obtaining different degrees of helical organization in gelatin is covalent functionalization, while a physical method for achieving the same goal is the variation of the drying conditions of gelatin solutions. Here we explored how the introduction of desaminotyrosine (DAT) and desaminotyrosyl tyrosine (DATT) linked to lysine residues of gelatin influenced the kinetics and thermodynamic equilibrium of the helicalization process of single and triple helices following different drying conditions. Drying at a temperature above the helix-to-coil transition temperature of gelatin (T > Tc, called vshort) generally resulted in gelatins with relatively lower triple helical content (Xc,t = 1−2%) than lower temperature drying (T < Tc, called vlong) (Xc,t = 8−10%), where the DAT(T) functional groups generally disrupted helix formation. While different helical contents affected the thermal transition temperatures only slightly, the mechanical properties were strongly affected for swollen hydrogels (E = 4−13 kPa for samples treated by vlong and E = 120−700 kPa for samples treated by vshort). This study shows that side group functionalization and different drying conditions are viable options to control the helicalization and macroscopic properties of gelatin-based materials. %0 journal article %@ 0391-3988 %A Zaupa, A.,Neffe, A.T.,Pierce, B.F.,Lendlein, A.,Hofmann, D. %D 2011 %J The International Journal of Artificial Organs %N 2 %P 139-151 %R doi:10.5301/IJAO.2010.6083 %T A molecular dynamic analysis of gelatin as an amorphous material: Prediction of mechanical properties of gelatin systems %U https://doi.org/10.5301/IJAO.2010.6083 2 %X Biomaterials are used in regenerative medicine for induced autoregeneration and tissue engineering. This is often challenging, however, due to difficulties in tailoring and controlling the respective material properties. Since functionalization is expected to offer better control, in this study gelatin chains were modified with physically interacting groups based on tyrosine with the aim of causing the formation of physical crosslinks. This method permits application-specific properties like swelling and better tailoring of mechanical properties. The design of the crosslink strategy was supported by molecular dynamic (MD) simulations of amorphous bulk models for gelatin and functionalized gelatins at different water contents (0.8 and 25 wt.-%). The results permitted predictions to be formulated about the expected crosslink density and its influence on equilibrium swelling behavior and on elastic material properties. The models of pure gelatin were used to validate the strategy by comparison between simulated and experimental data such as density, backbone conformation angle distribution, and X-ray scattering spectra. A key result of the simulations was the prediction that increasing the number of aromatic functions attached to the gelatin chain leads to an increase in the number of physical netpoints observed in the simulated bulk packing models. By comparison with the Flory-Rehner model, this suggested reduced equilibrium swelling of the functionalized materials in water, a prediction that was subsequently confirmed by our experimental work. The reduction and control of the equilibrium degree of swelling in water is a key criterion for the applicability of functionalized gelatins when used, for example, as matrices for induced autoregeneration of tissues. %0 conference lecture (invited) %@ %A Lendlein, A.,Neffe, A.,Wischke, C. %D 2011 %J 3rd International Conference on Smart Materials and Nanotechnology in Engineering, SMN 2011 %N %P %T Shape-memory Polymers as Platform Technology for Multifunctional Materials %U %X %0 report part %@ %A Neffe, A.T.,Behl, M.,Lendlein, A. %D 2011 %J Technologiereport - Regenerative Medizin in Berlin-Brandenburg %N %P 73-75 %T Polymere %U %X %0 conference lecture %@ %A Jung, F.,Neffe, A.T.,Lendlein, A. %D 2011 %J 38th Congress of the European Society for Artificial Organs, ESAO 2011 %N %P %T Hemocompatibility Testing of Polymers and Hemo-/Histocompatible Polymers %U %X %0 book part %@ %A Lendlein, A.,Wischke, C.,Kratz, K.,Heuchel, M.,Zotzmann, J.,Hiebl, B.,Neffe, A.,Behl, M. %D 2011 %J Comprehensive Biomaterials %N %P 479-496 %T Shape- Memory Polymers %U %X Medical devices such as implants, surgical instruments, extracorporal devices or wound covers, as well as controlled drug delivery systems (CDDS) require a specific combination of material properties and functions including, e.g., mechanical stability, biocompatibility, or biofunctionality. Polymeric biomaterials are of high relevance for such applications, as properties and functions can be tuned in a wide range by only small defined variations of their chemical or morphological structure. The rapid progress in surgical techniques, especially in minimally-invasive surgery, requires smart materials, which are capable of an active on-demand movement and which do not need to be removed in a second surgery. These challenges can be addressed by shape-memory polymers (SMPs) described in this chapter. SMPs are of high technological significance for biomedical applications as they enable on demand predefined changes in the shape of a device upon exposure to a suitable stimulus. Multifunctional materials are obtained when the shape-memory effect is combined with an additional function such as hydrolytic degradability, biofunctionality, and controlled drug release. Selected biomaterials with shape-memory capability are presented, including data on their biocompatibility. The potential of SMPs as a platform technology for biomedical applications is sketched by an overview on SMP-based medical devices being developed and the potential use of SMPs as matrix for CDDS. %0 conference lecture %@ %A Neffe, A.T.,Zaupa, A.,Lendlein, A. %D 2011 %J Bioorganik Symposium, Nachwuchsgruppenleitertreffen %N %P %T Gelatine mit definierten physikalischen Netzpunkten als Basis fuer supramolekulare, multifunktionale Biomaterialien %U %X %0 conference lecture %@ %A Neffe, A.T.,Pierce, B.F.,Blaszkiewicz, J.,Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting, Symposium V %N %P %T Quantifying Protein Adsorption to Physically Crosslinked Gelatin-Based Networks %U %X %0 conference poster %@ %A Wischke, C.,Loebler, M.,Neffe, A.T.,Hanh, B.D.,Zierke, M.,Sternberg, K.,Schmitz, K.-P.,Guthoff, R.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T A Blend of Poly(Epsilon-caprolactone) and Poly[(Epsilon-caprolactone)-co-glycolide] with Remarkable Mechanical Features and Wide Applicability as Biomaterial %U %X %0 conference poster %@ %A Neffe, A.T.,Zaupa, A.,Lendlein, A. %D 2011 %J 38th Congress of the European Society for Artificial Organs, ESAO 2011 %N %P %T Physical Crosslinking of Gelatin: A Supramolecular Approach to Biomaterials %U %X %0 journal article %@ 1946-4274 %A Santan, H.D.,Neffe, A.T.,Kamlage, S.,Lendlein, A. %D 2011 %J MRS Online Proceedings Library %N %P 226-233 %R doi:10.1557/opl.2012.703 %T Thermal Gelation and Stability of Pectin Grafted with PEPE %U https://doi.org/10.1557/opl.2012.703 %X Stimuli-sensitive materials can change properties upon exposure to an external stimulus. Thermoreversible gelation upon heating is one example for such a stimuli sensitivity. Here, it is of significance to tailor the tAransition temperature and to achieve large changes of G’ and the viscosity. Grafting of the thermosensitive poly(ethylene glycol-b-propylene glycol-b-ethylene glycol)s (PEPEs) to pectin was performed in order to investigate if tailoring of the sol-gel-transition temperature can be achieved by adjusting the grafting ratio. PEPEs were aminated and grafted to the polysaccharide via EDC coupling as shown by FTIR. The sol-gel transition of the pectin, PEPE, and the grafted system (PGP) was investigated by rheology. The gelation temperature (Tgel) of the system could be adjusted by varying the grafting density of PEPE onto pectin as well as by the concentration of the thermosensitive polymer in aqueous solution. A concentration of 15 – 20 wt% of the grafted system in water led to gelation temperatures in the range of 25 – 33 °C and the critical micelle concentration (CMC) and critical micelle temperature (CMT) of the grafted systems were determined by UV spectroscopy. The viscosity and the G’ increased by four orders of magnitudes at Tgel, which is comparable to PEPEs alone, but could be reached at lower PEPE concentrations. In the future, a thorough mechanistic investigation of the gelation process would be of interest. %0 conference poster %@ %A Santan, H.D.,Neffe, A.T.,Kamlage, S.,Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting, Symposium V %N %P %T Degradable Thermosensitive hydrogels based on grafted pectin or chondritin sulfate %U %X %0 journal article %@ 1022-1360 %A Neffe, A.T.,Kobuch, K.A.,Maier, M.,Feucht, N.,Lohmann, C.P.,Wolfstein, A.,Streufert, D.,Kamlage, S.,Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 229-235 %R doi:10.1002/masy.201100049 %T In vitro and in vivo Evaluation of a Multifunctional Hyaluronic acid based Hydrogel System for Local Application on the Retina %U https://doi.org/10.1002/masy.201100049 1 %X Conventional treatment of retinal detachment with laser and/or triamcinolon acetonide (TAAC) does not prevent loss of vision in all patients. Therefore, the development of degradable hydrogel patches covering retinal breaks was envisioned as alternative. Stable hydrogels could be formed by crosslinking hyaluronic acid with 1,2,3,4-diepoxybutane. Triamcinolone was diffusible in the gels. The hydrogels were slowly degrading, and mass loss during hydrolytic degradation was observed starting after three weeks. The sterilized gels showed excellent intraocular biocompatibility in vivo in rabbit eyes when applied as a patch on the retina. The good retinal adherence of the patch and absence of cellular growth and proliferation in and around the gel indicated the suitability as a material for a retinal patch to prevent cell-migration and proliferation after a retinal break and for local drug application. %0 journal article %@ 1022-1360 %A Lange, M.,Luetzow, K.,Neffe, A.T.,Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 40-48 %R doi:10.1002/masy.201100052 %T Synthesis and Characterization of Polyetherimides with 3-Methoxy-1,2-propanediol Moieties %U https://doi.org/10.1002/masy.201100052 1 %X Polyetherimides have been evaluated as non-toxic and steam-sterilizable and are therefore potentially suited for biomedical applications. To enable a broader range of potential applications, polyetherimides with lower Tg, higher elasticity at room temperature and better processability are required. Our concept was to explore, whether the incorporation of 3-methoxy-1,2-propanediol moieties in the main chain lead to a reduction of Tg and increase the elastic properties of the polymer compared to commercially available polyetherimides from 4,4′-(4,4′-isopropylidenediphenoxy)bis(phthalic anhydride) and 1,3-diaminobenzene. Two different monomers were synthesized and co-condensated with each other or using 4,4,4′-(4,4′-isopropylidenediphenoxy)bis(phthalic anhydride), respectively. The results proofed the successful synthesis and polymerization leading to polymers with molecular weights up to Mn = 6,400 g/mol. The polymers showed lowered Tg, resistance to heat up to 400 °C, tendencies to reduced contact angles and partially reduced E-moduli in comparison to the commercial polyetherimide ULTEM 1000. %0 conference poster %@ %A Lange, M.,Luetzow, K.,Neffe, A.T.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Synthesis and Characterization of a new Poly(ether imide) Based on 3-Methoxy-1,2-propandiol %U %X %0 journal article %@ 1022-1360 %A Roch, T.,Pierce, B.F.,Zaupa, A.,Jung, F.,Neffe, A.T.Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 182-189 %R doi:10.1002/masy.201100048 %T Reducing the Endotoxin Burden of Desaminotyrosine- and Desaminotyrosyl tyrosine-Functionalized Gelatin %U https://doi.org/10.1002/masy.201100048 1 %X Biomaterial-induced autoregeneration requires materials with distinct tailored mechanical and thermal properties, water uptake and swelling properties as well as degradation behavior. Furthermore, before any biomaterial can be applied in vivo, in vitro studies should be performed that confirm the suitability for such applications. One facet in this process is the evaluation of endotoxin loads and immunogenic response to the material to avoid an unspecific activation of the immune system, which otherwise might cause fever and could lead to life–threatening pathologies. In this study, gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) were investigated in terms of their endotoxin content and their potential to induce an inflammatory cytokine response in macrophages. Using the Limulus amebocyte lysate (LAL) test it could be shown that the endotoxin content was substantially reduced by using certified low endotoxin containing gelatin and performing the gelatin functionalization under cleanroom conditions. Furthermore, production of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor–alpha (TNFα) of an immune relevant macrophage cell line was significantly reduced for these materials. The survival of the macrophage cell line in the presence of DAT(T)-functionalized gelatins was not influenced by both materials. Therefore, DAT- and DATT-functionalized gelatins were shown to have passed the tests concerning immunological responses important for their applicability in vivo. %0 journal article %@ 1022-1360 %A Wischke, C.,Loebler, M.,Neffe, A.T.,Hanh, B.D.,Zierke, M.,Sternberg, K.,Schmitz, K.-P.,Guthoff, R.,Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 59-67 %R doi:10.1002/masy.201100050 %T A Blend of Poly(Epsilon-caprolactone) and Poly[(Epsilon-caprolactone)-co-glycolide] with Remarkable Mechanical Features and Wide Applicability as Biomaterial %U https://doi.org/10.1002/masy.201100050 1 %X Hydrolytic degradation of poly(ε-caprolactone) [PCL] can be enhanced by introduction of 8 wt.% glycolide leading to poly[(ε-caprolactone)-co-glycolide] (PCG), which has a low elongation at break εB of 4%. PCG/PCL blends (50/50 w/w) combined the advantageous features of its individual components such as mechanical properties similar to pure PCL (εB, Blend: 900 ± 230%; εB, PCL: 730 ± 50 at 20 °C), water uptake rates during degradation similar to pure PCG, and linear mass loss during bulk degradation independent from sample dimensions. The outcome of cytotoxicity studies was depending on the cell type with promising results, e.g., for Tenon fibroblasts. Easy processing of the blend was demonstrated by melt compression, foaming with CO2, and hot melt extrusion, suggesting a wide applicability as biomaterial, e.g., as drug carrier. %0 conference poster %@ %A Piluso, S.,Lendlein, A.,Neffe, A.T. %D 2011 %J Young European Biomaterial Scientists Designing a View for the Future, BioFuture 2011 %N %P %T Synthesis and Characterization of Gelatin Fragments Obtained by Controlled Degradation %U %X %0 journal article %@ 1022-1360 %A Piluso, S.,Weigel, T.,Lendlein, A.,Neffe, A.T. %D 2011 %J Macromolecular Symposia %N 1 %P 199-204 %R doi:10.1002/masy.201100054 %T Synthesis and Characterization of Gelatin Fragments Obtained by Controlled Degradation %U https://doi.org/10.1002/masy.201100054 1 %X Telechelic oligomers are attractive starting materials for the preparation of materials with tailorable properties. Here, peptide chains with defined molecular weight were obtained by controlled degradation of gelatin with hydroxylamine, which resulted in the cleavage of asparaginyl-glycine bonds and formation of new aspartyl hydroxamates and amino endgroups. The reaction of gelatin with hydroxylamine resulted in fragments with molecular weights of 15, 25, 37, and 50 kDa (determined by SDS-PAGE) independently of the reaction time and conditions. The fragment mixture showed typical single and triple helical organization in WAXS spectra, but rheological studies showed lower G′ and G″ values for gels from the fragment mixture than from gelatin, and lower gel-sol transitions temperatures. A more narrow distribution was found for the fragment mixture (Mn=25 kDa, PDI=1.4) than for commercial gelatin. %0 conference poster %@ %A Piluso, S.,Lendlein, A.,Neffe, A.T. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Synthesis and Characterization of Gelatin Fragments Obtained by Controlled Degradation %U %X %0 conference poster %@ %A Lange, M.,Luetzow, K.,Neffe, A.T.,Lendlein, A. %D 2011 %J Young European Biomaterial Scientists Designing a View for the Future, BioFuture 2011 %N %P %T Polyetherimides with 3-methoxy-1,2-propanediol moieties %U %X %0 journal article %@ 1022-1360 %A Federico, S.,Lendlein, A.,Neffe, A.T. %D 2011 %J Macromolecular Symposia %N 1 %P 205-212 %R doi:10.1002/masy.201100055 %T Synthesis and Characterization of a Telechelic Peptide as a Precursor for Supramolecular Networks %U https://doi.org/10.1002/masy.201100055 1 %X A peptide showing propensity for the adoption of β-sheet conformation was synthesized in order to develop a defined molecular building block as part of a toolbox for the development of polymer networks based on supramolecular interactions. The peptide was synthesized by microwave-assisted solid phase peptide synthesis and the purification was performed by Reversed Phase-High Performance Liquid Chromatography (RP-HPLC), from which a purity higher than 95 mol-% was obtained. The calculated mass was confirmed by Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry (MALDI-ToF-MS). Further characterization of the peptide was performed by IR and 2D TOCSY, NOESY, and HSQC NMR spectroscopy, which confirmed the identity and the sequence of the peptide. %0 conference poster %@ %A Federico, S.,Lendlein, A.,Neffe, A.T. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Supramolecular Networks formed by Biological Rcognition of Collagen and a Peptide Grafted to Hyaluronic Acid %U %X %0 conference lecture %@ %A Neffe, A.T.,Zaupa, A.,Pierce, B.F.,Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting %N %P %T Knowledge-Based Design and Tailoring of Gelatin-Based Hydrogels by Functionalization with Tyrosine-Derived Groups %U %X %0 journal article %@ 0391-3988 %A Piluso, S.,Hiebl, B.,Gorb, S.N.,Kovalev, A.,Lendlein, A.,Neffe, A.T. %D 2011 %J The International Journal of Artificial Organs %N 2 %P 192-197 %R doi:10.5301/IJAO.2011.6394 %T Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties %U https://doi.org/10.5301/IJAO.2011.6394 2 %X Biopolymers of the extracellular matrix are attractive starting materials for providing degradable and biocompatible biomaterials. In this study, hyaluronic acid-based hydrogels with tunable mechanical properties were prepared by the use of copper- catalyzed azide-alkyne cycloaddition (known as “click chemistry”). Alkyne-functionalized hyaluronic acid was crosslinked with linkers having two terminal azide functionalities, varying crosslinker density as well as the lengths and rigidity of the linker molecules. By variation of the crosslinker density and crosslinker type, hydrogels with elastic moduli in the range of 0.5-4 kPa were prepared. The washed materials contained a maximum of 6.8 mg copper per kg dry weight and the eluate of the gel crosslinked with diazidostilbene did not show toxic effects on L929 cells. The hyaluronic acid-based hydrogels have potential as biomaterials for cell culture or soft tissue regeneration applications. %0 journal article %@ 1946-4274 %A Neffe, A.T.,Pierce, B.F.,Blaszkiewicz, J.,Lendlein, A. %D 2011 %J MRS Online Proceedings Library %N %P 196-201 %R doi:10.1557/opl.2012.476 %T Quantifying Protein Adsorption to Physically Crosslinked Gelatin-Based Networks %U https://doi.org/10.1557/opl.2012.476 %X Physically crosslinked hydrogels based on gelatin functionalized with desaminotyrosine (DAT) (giving Gel-DAT) or desaminotyrosyl tyrosine (DATT) (resulting in Gel-DATT) have shown high potential as biomaterials. Here, protein adsorption to the functionalized gelatins in comparison to gelatin was quantified to see if the functionalization and chain organization of gelatins has an influence on the amount of proteins being adsorbed. For this purpose, gelatin, Gel-DAT, and Gel-DATT were incubated with water or aq. solutions of bovine serum albumin (BSA), fibrinogen, or fibronectin, respectively, at physiological concentrations. Protein concentrations in the supernatant were determined with the bicinchoninic acid (BCA) assay before and after the contact. BSA adsorption to the materials was influenced as well by the hydrophobicity of the material as the degree of swelling, with the observation that higher protein concentrations led to lower protein adsorption. The highest amount of fibronectin was adsorbed to Gel-DAT, followed by gelatin and Gel-DATT, with only small differences for different initial protein concentrations. Fibrinogen adsorption increased with increasing concentration. In the future, adsorption studies based on specific antibody-based techniques might enable quantification of the proteins also in competition assays and direct quantification of adsorbed material. %0 conference lecture %@ %A Piece, B.F.,Neffe, A.T.,Lendlein, A. %D 2011 %J MRS Fall 2011 Meeting, Symposium V %N %P %T Photocrosslinked Co-Networks from Glycidylmethacrylated Gelatin and Poly(ethylene glycol) (Di)Methacrylates %U %X %0 journal article %@ 1022-1352 %A Neffe, A.T.,Tronci, G.,Alteheld, A.,Lendlein, A. %D 2010 %J Macromolecular Chemistry and Physics %N 2 %P 182-194 %R doi:10.1002/macp.200900441 %T Controlled Change of Mechanical Properties during Hydrolytic Degradation of Polyester Urethane Networks %U https://doi.org/10.1002/macp.200900441 2 %X Polyester urethane networks are versatile polymer systems as it is possible to tailor their mechanical properties and their hydrolytic degradation profile. For biomedical applications, the biodegradability as well as the thermomechanical properties of the polymer networks during the course of degradation is of importance. Therefore, we investigated the change of thermomechanical properties of networks based on star-shaped precursors of rac-dilactide and diglycolide, -caprolactone, or p-dioxanone, respectively, during hydrolytic degradation. Degradation rate and mechanical properties of the polymer networks were tailored by crosslink density, comonomers, and by changing the glass transition temperature. Most importantly, the degradation of the networks led to a controlled, step-by-step change of the mechanical properties of the networks. %0 book part %@ %A Wischke, C.,Neffe, A.,Lendlein, A. %D 2010 %J Advances in Polymer Science - Shape-memory Polymers %N %P 177-206 %R doi:10.1007/12_2009_29 %T Controlled Drug Release from Biodegradable Shape-Memory Polymers %U https://doi.org/10.1007/12_2009_29 %X Biodegradable shape-memory polymers (SMPs) have attracted significant interest for biomedical applications. Modern concepts for biofunctional implants often comprise the controlled release of bioactive compounds to gain specific,biofunctionalities. Therefore, a general strategy has been suggested for polymer systems combining degradability and shape-memory capability with controlled release,of drugs. This chapter provides a detailed description of the molecular basis for such multifunctional SMPs including the selection of building blocks, the polymer morphology, and the three dimensional architecture. Moreover, drug loading and release, drug effects on thermomechanical properties of SMPs, and drug release patterns in a physiological environment are described and potential applications in minimally-invasive surgery are discussed. %0 conference paper %@ %A Luetzow, K.,Neffe, A.,Lendlein, A. %D 2010 %J Medical Device Materials V, Proceedings from the Materials Processes for Medical Devices Conference, MPMD 2009 %N %P 169-174 %T Developing Cell Selectivities of Acrylonitrile Based Copolymers and Porous Bodies from Poly(ether imide) %U %X %0 conference poster %@ %A Wischke, C.,Weigel, J.,Neffe, A.T.,Lendlein, A. %D 2010 %J Biodegradable Polymers as Biomaterials, 459th WE-Heraeus-Seminar %N %P %T Understanding instability and rupture of polyalkyl 2-cyanoacrylate capsules %U %X %0 conference poster %@ %A Wischke, C.,Neffe, A.T.,Lendlein, A. %D 2010 %J GDCh Biannual Meeting of the GDCh-Division Macromolecular Chemistry and Polydays %N %P %T Copolyesterdimethacrylate-derived Networks combine Shape-memory, Biodegradability, and Controlled Drug Release %U %X %0 journal article %@ 0928-0987 %A Wischke, C.,Neffe, A.T.,Steuer, S.,Lendlein, A. %D 2010 %J European Journal of Pharmaceutical Sciences %N 11 %P 136-147 %R doi:10.1016/j.ejps.2010.06.003 %T Comparing techniques for drug loading of shape-memory polymer networks–effect on their functionalities %U https://doi.org/10.1016/j.ejps.2010.06.003 11 %X A family of oligo[(var epsilon-caprolactone)-co-glycolide]dimethacrylate (oCG-DMA) derived networks of different glycolide content as well as precursor molecular weight has been synthesized by crosslinking oCG-DMA, providing matrices of different hydrophilicity, network density, and morphology at body temperature. Such networks were loaded with a hydrophilic model drug, ethacridine lactate, either before crosslinking or afterwards by swelling in drug solution. Disadvantageous alterations of the shape-memory functionality and degradation characteristics were observed only in few loaded materials. Loading by swelling generally resulted in low payloads, which slightly increased for more hydrophilic polymer networks, and a substantial burst and fast subsequent release for all investigated materials. Loading before crosslinking gave almost no burst and higher subsequent release rates over longer periods of time. Overall, depending on the needs of a specific application, a material from this polymer family with the desired mechanical properties, shape-memory functionality, and degradation pattern can be selected and combined with drugs when considering that i) loading by swelling is best suited for applications that require high initial doses and ii) loading before crosslinking allows easy variation of payloads and low burst release for therapeutics that are non-sensitive to chemical alterations during crosslinking. %0 conference lecture %@ %A Wischke, C.,Neffe, A.T.,Lendlein, A. %D 2010 %J Biodegradable Polymers as Biomaterials, 459th WE-Heraeus-Seminar %N %P %T Multifunctional polymers combining shape-memory, drug release, and biodegradability %U %X %0 journal article %@ 0959-9428 %A Tronci, G.,Neffe, A.T.,Pierce, B.F.,Lendlein, A. %D 2010 %J Journal of Materials Chemistry %N 40 %P 8875-8884 %R doi:10.1039/C0JM00883D %T An Entropy–Elastic Gelatin-based Hydrogel System %U https://doi.org/10.1039/C0JM00883D 40 %X Gelatin is a non-immunogenic and degradable biopolymer, which is widely applied in the biomedical field e.g. for drug capsules or as absorbable hemostats. However, gelatin materials present limited and hardly reproducible mechanical properties especially in aqueous systems, particularly caused by the uncontrollable partial renaturation of collagen-like triple helices. Therefore, mechanically demanding applications for gelatin-based materials, such as vascular patches, i.e. hydrogel films that seal large incisions in vessel walls, and for induced autoregeneration, are basically excluded if this challenge is not addressed. Through the synthesis of a defined chemical network of gelatin with hexamethylene diisocyanate (HDI) in DMSO, the self-organization of gelatin chains could be hindered and amorphous gelatin films were successfully prepared having Young's moduli of 60–530 kPa. Transferring the crosslinking reaction with HDI and, alternatively, ethyl lysine diisocyanate (LDI), to water as reaction medium allowed the tailoring of swelling behaviour and mechanical properties by variation of crosslinker content while suppressing the formation of helices. The hydrogels had Young's moduli of 70–740 kPa, compressive moduli of 16–48 kPa, and degrees of swelling of 300–800 vol%. Test reactions investigated by ESI mass spectrometry allowed the identification and quantification of reaction products of the crosslinking reaction. The HDI crosslinked networks were stabilized by direct covalent crosslinks (ca. 10 mol%), supported by grafting (50 mol%) and blending of hydrophobic oligomeric chains. For the LDI-based networks, less crosslinked (3 mol%) and grafted species (5 mol%) and much higher amounts of oligomers were observed. The adjustable hydrogel system enables the application of gelatin-based materials in physiological environments. %0 journal article %@ 1022-1336 %A Neffe, A.T.,Zaupa, A.,Pierce, B.F.,Hofmann, D.,Lendlein, A. %D 2010 %J Macromolecular Rapid Communications %N 17 %P 1534-1539 %R doi:10.1002/marc.201000274 %T Knowledge-Based Tailoring of Gelatin-Based Materials by Functionalization with Tyrosine-Derived Groups %U https://doi.org/10.1002/marc.201000274 17 %X Molecular models of gelatin-based materials formed the basis for the knowledge-based design of a physically cross-linked polymer system. The computational models with 25 wt.-% water content were validated by comparison of the calculated structural properties with experimental data and were then used as predictive tools to study chain organization, cross-link formation, and estimation of mechanical properties. The introduced tyrosine-derived side groups, desaminotyrosine (DAT) and desaminotyrosyl tyrosine (DATT), led to the reduction of the residual helical conformation and to the formation of physical net-points by π–π interactions and hydrogen bonds. At 25 wt.-% water content, the simulated and experimentally determined mechanical properties were in the same order of magnitude. The degree of swelling in water decreased with increasing the number of inserted aromatic functions, while Young's modulus, elongation at break, and maximum tensile strength increased. %0 journal article %@ 1616-5187 %A Wischke, C.,Neffe, A.T.,Steuer, S.,Engelhardt, E.,Lendlein, A. %D 2010 %J Macromolecular Bioscience %N 9 %P 1063-1072 %R doi:10.1002/mabi.201000089 %T AB-polymer Networks with Cooligoester and Poly(Eta-butyl acrylate) Segments as a Multifunctional Matrix for Controlled Drug Release %U https://doi.org/10.1002/mabi.201000089 9 %X Semi-crystalline AB-copolymer networks from oligo[(ε-caprolactone)-co-glycolide]dimethacrylates and n-butylacrylate have recently been shown to exhibit a shape-memory functionality, which may be used for self-deploying and anchoring of implants. In this study, a family of such materials differing in their molar glycolide contents χG was investigated to determine structure–property functional relationships of unloaded and drug loaded specimens. Drug loading and release were evaluated, as well as their degradation behavior in vitro and in vivo. Higher χG resulted in higher loading levels by swelling and a faster release of ethacridine lactate, lower melting temperature of polymer crystallites, and a decrease in shape fixity ratio of the programmed temporary shape. For unloaded networks, the material behavior in vivo was independent of the mechanical load associated with different implantation sites and agreed well with data from in vitro degradation studies. Thus, AB networks could be used as novel matrices for biofunctional implants, e.g., for urogenital applications, which can self-anchor in vivo and provide mechanical support, release drugs, and finally degrade in the body to excretable fragments. %0 journal article %@ 1617-9439 %A Neffe, A.T.,Lendlein, A. %D 2010 %J Physik-Journal %N 10 %P 56 %T Abbaubare Polymere als Biomaterialien %U 10 %X No abstract %0 conference poster %@ %A Zaupa, A.,Neffe, A.T.,Pierce, B.F.,Hofmann, D.,Lendlein, A. %D 2010 %J Polymers in Biomedicine and Electronics %N %P %T Knowledge-Based Approach to Tailorable Gelatin-Based Materials Functionalized with Tyrosine-Derived Moieties %U %X %0 conference poster %@ %A Piluso, S.,Lendlein, A.,Neffe, A.T. %D 2010 %J Biodegradable Polymers as Biomaterials, 459th WE-Heraeus-Seminar %N %P %T Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties %U %X %0 conference lecture %@ %A Luetzow, K.,Neffe, A.,Lendlein, A. %D 2009 %J Materials Processes for Medical Devices Conference, MPMD 2009 %N %P %T Developing Cell Selectivities of Acrylonitrile Based Copolymers and Porous Bodies from Poly(ether imide) %U %X %0 journal article %@ 0044-8249 %A Abell, A.D.,Jones, M.A.,Coxon, J.M.,Morton, J.D.,Aitken, S.G.,Mc Nabb, S.B.,Lee, H.Y.Y.,Mehrtens, J.M.,Alexander, N.A.,Stuart, B.G.,Neffe, A.T.,Bickerstaffe, R. %D 2009 %J Angewandte Chemie %N 8 %P 1483-1486 %R doi:10.1002/ange.200805014 %T Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors %U https://doi.org/10.1002/ange.200805014 8 %X Entwurf und Synthese einer Reihe von makrocyclischen Gerüsten, die eine -Strang-ähnliche Peptidrückgrat-Konformation bevorzugen, führten zu wirksamen und selektiven Inhibitoren von Calpain 2. Der Makrocyclus 1 verzögerte die calciuminduzierte Eintrübung von Schafslinsen in Kultur und dient als Leitstruktur für die Entwicklung eines Wirkstoffs zur Behandlung von grauem Star. %0 conference lecture %@ %A Wischke, C.,Neffe, A.,Steuer, S.,Lendlein, A. %D 2009 %J 36th Annual Meeting and Exposition of the Controlled Release Society %N %P %T Amorphous Polymer Network combining Three Functionalities – Shape-memory, Biodegradability, and Drug Release %U %X %0 conference lecture %@ %A Neffe, A.T.,Steuer, S.,Hanh, B.-D.,Lendlein, A. %D 2009 %J 4th World Congress on Regenerative Medicine %N %P %T Polymer networks combining three functionalities – shape-memory, biodegradability, and drug release %U %X %0 journal article %@ 0935-9648 %A Neffe, A.T.,Hanh, B.D.,Steuer, S.,Lendlein, A. %D 2009 %J Advanced Materials %N 32-33 %P 3394-3398 %R doi:10.1002/adma.200802333 %T Polymer Networks Combining Controlled Drug Release, Biodegradation, and Shape Memory Capability %U https://doi.org/10.1002/adma.200802333 32-33 %X No abstract %0 conference paper %@ %A Wischke, C.,Neffe, A.,Steuer, S.,Lendlein, A. %D 2009 %J Active Polymers - MRS Symposium Proceedings, MRS Spring Meeting 2009 %N %P NN11-34 %R doi:10.1557/PROC-1190-NN11-34 %T Amorphous Polymer Networks Combining Three Functionalities - Shape-Memory, Biodegradability, and Drug Release %U https://doi.org/10.1557/PROC-1190-NN11-34 %X %0 conference lecture %@ %A Wischke, C.,Neffe, A.,Steuer, S.,Lendlein, A. %D 2009 %J MRS Spring Meeting 2009 %N %P %T Amorphous Polymer Networks Combining Three Functionalities - Shape-Memory, Biodegradability, and Drug Release %U %X %0 conference poster %@ %A Wischke, C.,Neffe, A.,Steuer, S.,Lendlein, A. %D 2009 %J Controlled Release Society Annual Meeting & Exposition 2009 %N %P %T Amorphous polymer networks combining three functionalities – Shape-memory, biodegradability, and drug release %U %X %0 conference lecture (invited) %@ %A Lendlein, A.,Luetzow, K.,Hiebl, B.,Lange, M.,Weigel, T.,Seifert, B.,Klein, F.,Tronci, G.,Neffe, A. %D 2009 %J Organotyp Tissue Culture Techniques for Substance Evaluation, DECHEMA/BioTop Potsdam Symposium %N %P %T Biomaterials and Scaffolds for Tissue Regeneration %U %X %0 conference lecture %@ %A Neffe, A.T. %D 2009 %J 18. Nachwuchswissenschaftler-Symposium Bioorganische Chemie %N %P %T Bioabbaubare Polymernetzwerke mit kontrollierter Wirkstofffreisetzung und Formgedaechtnis %U %X %0 conference lecture (invited) %@ %A Lendlein, A.,Tronci, G.,Zaupa, A.,Pierce, B.,Neffe, A.,Cui, J.,Kratz, K. %D 2009 %J Biomechanics and Biology of Bone Healing, International Symposium 2009 %N %P %T Biomimetic Scaffolds supporting Bone Regeneration in Critical Defects %U %X %0 lecture %@ %A Neffe, A.,Lendlein, A. %D 2009 %J %N %P %T Shape-Memory Polymers %U %X %0 conference paper %@ %A Neffe, A.T.,Hanh, B.D.,Steuer, S.,Wischke, C.,Lendlein, A. %D 2009 %J Active Polymers - MRS Symposium Proceedings, MRS Spring Meeting 2009 %N %P NN06-02 %R doi:10.1557/PROC-1190-NN06-02 %T Thermomechanical Properties and Shape-Memory Capability of Drug Loaded Semi-Crystalline Polyestermethacrylate Networks %U https://doi.org/10.1557/PROC-1190-NN06-02 %X %0 conference poster %@ %A Neffe, A.T.,Hanh, B.D.,Steuer, S.,Wischke, C.,Lendlein, A. %D 2009 %J MRS Spring Meeting 2009 %N %P %T Thermomechanical Properties and Shape-Memory Capability of Drug Loaded Semi-Crystalline Polyestermethacrylate Networks %U %X %0 lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2009 %J %N %P %T Introduction to Peptide Synthesis %U %X %0 conference lecture (invited) %@ %A Neffe, A.T. %D 2009 %J 3. BMBF-Projektforum Biotechnologie %N %P %T Neuer Therapieansatz in der Glaukombehandlung - Drainagesystem als Grundlage fuer das trabekelwerk-Tissue-Engineering %U %X %0 lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2009 %J %N %P %T Wirkstoffdesign und Freisetzungssysteme %U %X %0 journal article %@ 0168-3659 %A Wischke, C.,Neffe, A.,Steuer, S.,Lendlein, A. %D 2009 %J Journal of Controlled Release %N 3 %P 243-250 %R doi:10.1016/j.jconrel.2009.05.027 %T Evaluation of a degradable shape-memory polymer network as matrix for controlleddrug release %U https://doi.org/10.1016/j.jconrel.2009.05.027 3 %X Degradable shape-memory polymers are multifunctional materials with broad applicability for medical,devices. They are designed to acquire their therapeutically relevant shape and mechanical properties after,implantation. In this study, the potential of a completely amorphous shape-memory polymer matrix for,controlled drug release was comprehensively characterized according to a four step general strategy which,provides concepts for validating multifunctional materials for pharmaceutical applications. Independent,functionalities are thereby crucial for fully exploiting the potential of the materials. The copolyester urethane,network was synthesized by crosslinking star-shaped tetrahydroxy telechelics of oligo[(rac-lactide)-coglycolide],with an aliphatic diisocyanate. In step 1 of the four step characterization procedure, this material,showed the thermal and mechanical properties, which are required for the shape-memory effect under,physiological conditions. Shape recovery could be realized by a one-step or a multi-step methodology. In,step 2, feasibility of drug loading of pre-formed shape-memory networks has been demonstrated with drugs,of different hydrophobicities. The presence of drugs did not disturb the material's functionalities directly,after loading (step 3) and under release conditions (step 4). A predictable release of about 90% of the payload,in 80 days was observed. Overall, the synthesized amorphous polymer network showed three independent,functionalities, i.e., a shape-memory effect combined with biodegradability and controlled drug release. %0 conference poster %@ %A Neffe, A.T.,Meyer, B. %D 2008 %J Carbohydrates at the Interfaces of Biology, Medicine and Materials Science, 3rd EraChemistry Flash Conference %N %P %T Glycosylation Enhances the Calculated Binding Affinity of GP120 Derived Peptides and Peptidomimetics to CD4 %U %X %0 journal article %@ 0968-0896 %A Jones, M.A.,Abell, A.D.,Morton, J.D.,Coxon, J.M.,McNabb, S.B.,Lee, H.Y.-Y.,Aitken, S.G.,Mehrtens, J.M.,Robertson, L.J.G.,Neffe, A.T.,Gately, K.,Wood, J.M. %D 2008 %J Bioorganic & Medicinal Chemistry %N 14 %P 6911-6923 %R doi:10.1016/j.bmc.2008.05.048 %T Synthesis, biological evaluation and molecular modeling of N-heterocyclic dipeptide aldehydes as selective calpain inhibitors %U https://doi.org/10.1016/j.bmc.2008.05.048 14 %X A series of N-heterocyclic dipeptide aldehydes 4–13 have been synthesised and evaluated as inhibitors of ovine calpain 1 (o-CAPN1) and ovine calpain 2 (o-CAPN2). 5-Formyl-pyrrole 9 (IC50 values of 290 and 25 nM against o-CAPN1 and o-CAPN2, respectively) was the most potent and selective o-CAPN2 inhibitor, displaying >11-fold selectivity. The amino acid sequences of o-CAPN1 and o-CAPN2 have been determined. Because of the lack of available structural information on the ovine calpains, in silico homology models of the active site cleft of o-CAPN1 and o-CAPN2 were developed based on human calpain 1 (h-CAPN1) X-ray crystal structure (PDB code 1ZCM). These models were used to rationalise the observed SAR for compounds 4–13 and the selectivity observed for 9. The o-CAPN2 selective inhibitor 9 (CAT0059) was assayed in an in vitro ovine lens culture system and shown to successfully protect the lens from calcium-induced opacification. %0 conference lecture (invited) %@ %A Lendlein, A.,Luetzow, K.,Madbouly, S.,Weigel, T.,Reiche, J.,Kratz, K.,Tronci, G.,Neffe, A.T. %D 2008 %J Biomechanics and Biology of Bone Healing, Symposium und Gruendung des Julius Wolff Instituts %N %P %T Formation of Foams from Biodegradable Artificial Materials and Biopolymers %U %X %0 conference poster %@ %A Kim, S.W.,Hudson, I.L.,Neffe, A.T.,Abell, A.D. %D 2008 %J International Society for Bayesian Analysis, 9th World Meeting %N %P %T Bayesian multivariate mixture (BMM) model: An upgraded classification method %U %X %0 conference lecture (invited) %@ %A Neffe, A.T. %D 2008 %J Nachwachsende Rohstoffe in der Industrie, Kreativworkshop Biopolymere %N %P %T Biopolymere im Bereich biomedizinische Therapieentwicklungen %U %X %0 conference lecture %@ %A Neffe, A.T.,Tronci, G.,Roessle, M.,Lendlein, A. %D 2008 %J 17. Nachwuchswissenschaftler-Symposium Bioorganische Chemie %N %P %T Dimensionally Stable Scaffolds from Gelatin-Based Polymer System %U %X %0 lecture %@ %A Neffe, A.T.,Lendlein, A. %D 2008 %J %N %P %T Wirkstoffdesign und Freisetzungssysteme %U %X %0 lecture %@ %A Neffe, A.T. %D 2008 %J %N %P %T Advanced Topics in Polymer Synthesis – Biopolymers %U %X %0 conference poster %@ %A Neffe, A.T.,Tronci, G.,Roessle, M.,Lendlein, A. %D 2008 %J MRS Fall Meeting 2008, SESSION HH5: Poster Session: Functional Materials and Drug Delivery Systems %N %P %T Tailored Scaffolds from a Gelatin-based Polymer System: Influence of the Molecular Architecture on Material Properties %U %X %0 conference lecture %@ %A Neffe, A.T.,Hanh, B.D.,Steuer, S.,Lendlein, A. %D 2008 %J MRS Fall Meeting 2008 %N %P %T Triple-Functional Polymer Networks Combining Controlled Drug Release, Biodegradation, and Shape Memory Capability %U %X %0 conference lecture %@ %A Neffe, A.T.,Hanh, B.D.,Steuer, S.,Kelch, S.,Lendlein, A. %D 2008 %J Materials Science and Engineering, MSE 2008 %N %P %T Triple-Functional Polymer Networks Combining Controlled Drug Release, Biodegradation, and Shape Memory Capability %U %X %0 journal article %@ 0022-2623 %A Neffe, A.T.,Bilang, M.,Grueneberg, I.,Meyer, B. %D 2007 %J Journal of Medicinal Chemistry %N 15 %P 3482-3488 %R doi:10.1021/jm070206b %T Rational Optimization of the Binding Affinity of CD4 Targeting Peptidomimetics With Potential Anti HIV Activity %U https://doi.org/10.1021/jm070206b 15 %X We recently reported the design and synthesis of a CD4 binding peptidomimetic with potential as HIV entry inhibitor. Variation of side chains and amino terminus provided first structure-activity relationships and confirmed the activity of the compounds as well as the correctness of our approach [Neffe, A. T.; Bilang, M.; Meyer, B. Org. Biomol. Chem. 2006, 4, 3259-3267]. Here we describe optimizations at the carboxy terminus of the peptidomimetic CD4 ligands resulting in the highest binding affinity of KD = 6 M for compound 4 determined with surface plasmon resonance (SPR). Saturation transfer difference NMR experiments with two peptidomimetics give binding constants similar to the SPR experiments and verified the ligand binding epitope. The higher proteolytic stability of the peptidomimetics compared to the lead peptide is demonstrated in a pronase digestion assay. Comparison of modeling and analytical data shows good agreement of theoretical and practical experiments. %0 conference lecture (invited) %@ %A Neffe, A.T. %D 2007 %J Wissenschaftliches Kolloquium am Zentralinstitut fuer Laboratoriumsmedizin und Pathobiochemie %N %P %T Bioaktive Peptide und Glycokonjugate - HIV-Entry-Inhibitoren, Calpain-Inhibitoren und Biomimetik %U %X %0 journal article %@ 0022-2623 %A Abell, A.D.,Jones, M.A.,Neffe, A.T.,Aitken, S.G.,Cain, T.P.,Payne, R.J.,McNabb, S.B.,Coxon, J.M.,Stuart, B.G.,Pearson, D.,Lee, H.Y.-Y.,Morton, J.D. %D 2007 %J Journal of Medicinal Chemistry %N 12 %P 2916-2920 %R doi:10.1021/jm061455n %T Investigation into the P3 Binding Domain of m-Calpain Using Photoswitchable Diazo- and Triazene-dipeptide Aldehydes: New Anticataract Agents %U https://doi.org/10.1021/jm061455n 12 %X The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d, 10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds deep in the S3 pocket of calpain. All compounds are potent inhibitors of m-calpain, with 8b being the most active (IC50 of 35 nM). The diazo-containing inhibitors 8a, 8c, and 10a were irradiated at 340 nm to give a photostationary state enriched in the (Z)-isomer, and in all cases, these were less active. The most water soluble triazene 17a (IC50 of 90 nM) retards calpain-induced cataract formation in lens culture. %0 conference lecture %@ %A Wischke, C.,Neffe, A.,Steuer, S.,Lendlein, A. %D 2007 %J 6th International Nanomedicine and Drug Delivery Symposium, Nano DDS 2008 %N %P %T Evaluation of a degradable shape-memory polymer network as matrix for controlleddrug release %U %X Degradable shape-memory polymers are multifunctional materials with broad applicability for medical,devices. They are designed to acquire their therapeutically relevant shape and mechanical properties after,implantation. In this study, the potential of a completely amorphous shape-memory polymer matrix for,controlled drug release was comprehensively characterized according to a four step general strategy which,provides concepts for validating multifunctional materials for pharmaceutical applications. Independent,functionalities are thereby crucial for fully exploiting the potential of the materials. The copolyester urethane,network was synthesized by crosslinking star-shaped tetrahydroxy telechelics of oligo[(rac-lactide)-coglycolide],with an aliphatic diisocyanate. In step 1 of the four step characterization procedure, this material,showed the thermal and mechanical properties, which are required for the shape-memory effect under,physiological conditions. Shape recovery could be realized by a one-step or a multi-step methodology. In,step 2, feasibility of drug loading of pre-formed shape-memory networks has been demonstrated with drugs,of different hydrophobicities. The presence of drugs did not disturb the material's functionalities directly,after loading (step 3) and under release conditions (step 4). A predictable release of about 90% of the payload,in 80 days was observed. Overall, the synthesized amorphous polymer network showed three independent,functionalities, i.e., a shape-memory effect combined with biodegradability and controlled drug release. %0 conference lecture %@ %A Neffe, A.T.,Meyer, B. %D 2007 %J 16. Nachwuchswissenschaftler-Symposium Bioorganische Chemie %N %P %T Design, Synthesis, and Analysis of CD4 Binding Peptidomimetics – Development of HIV Entry Inhibitors %U %X %0 journal article %@ 1048-6690 %A Neffe, A.T.,Lendlein, A. %D 2007 %J Medical Device Technology %N 6 %P 14-19 %T Tailoring established polymers for medical applications %U 6 %X Polymers can be tailored for specific biomedical applications by synthesis, processing or surface modification. Knowledge-based choice of comonomers for acrylonitrile based copolymers influences the interaction profile with specific cell lines and blood. Processing or surface modification of poly(ether imides) results in materials having complex three-dimensional structures and/or specific adsorption profiles. Potential applications are dialysis, gas separation, cell/tissue systems, apheresis, and bioreactors. %0 lecture %@ %A Neffe, A.T. %D 2007 %J %N %P %T Biopolymers %U %X %0 conference lecture %@ %A Neffe, A.T. %D 2007 %J GDCh-Vortrag Ortsverband Potsdam %N %P %T Modelling und Synthese von peptidomimetischen Wirkstoffen -HIV-Entry-Inhibitoren und Calpain Inhibitoren %U %X %0 conference lecture %@ %A Neffe, A.T. %D 2006 %J Seminar der Universitaets-Augenklinik %N %P %T Calpain Inhibitoren zur Behandlung von Katarakten %U %X %0 conference lecture %@ %A Kim, S.W.,Hudson, I.L.,Neffe, A.T.,Abell, A.D. %D 2006 %J Bioinformatics Summer Symposium THEME, Recent Discoveries and New Challenges %N %P %T Bayes Mix Identification of Important Docking Parameters, Exemplified for Calpain Inhibitors %U %X