TY  - JOUR
A1  - Zaupa, Alessandro
A1  - Neffe, Axel T.
A1  - Pierce, Benjamin F.
A1  - Lendlein, Andreas
A1  - Hofmann, Dieter
T1  - A molecular dynamic analysis of gelatin as an amorphous material  Prediction of mechanical properties of gelatin systems
JF  - The international journal of artificial organs
N2  - 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.
KW  - Physical Network
KW  - Biopolymer material
KW  - Molecular modeling
KW  - Gelatin
Y1  - 2011
U6  - https://doi.org/10.5301/IJAO.2010.6083
SN  - 0391-3988
VL  - 34
IS  - 2
SP  - 139
EP  - 151
PB  - Wichtig
CY  - Milano
ER  - 
TY  - JOUR
A1  - Zou, Jie
A1  - Wang, Weiwei
A1  - Neffe, Axel T.
A1  - Xu, Xun
A1  - Li, Zhengdong
A1  - Deng, Zijun
A1  - Sun, Xianlei
A1  - Ma, Nan
A1  - Lendlein, Andreas
T1  - Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel)
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - 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 mu m after 4 days, and distributed in the whole scaffold (2mm 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.
KW  - Mesenchymal stem cells
KW  - gelatin based scaffold
KW  - adipose tissue regeneration
KW  - adipogenic differentiation
Y1  - 2017
U6  - https://doi.org/10.3233/CH-179210
SN  - 1386-0291
SN  - 1875-8622
VL  - 67
IS  - 3-4
SP  - 297
EP  - 307
PB  - IOS Press
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Izraylit, Victor
A1  - Hommes-Schattmann, Paul Jacob
A1  - Neffe, Axel T.
A1  - Gould, Oliver E. C.
A1  - Lendlein, Andreas
T1  - Alkynyl-functionalized chain-extended PCL for coupling to biological molecules
JF  - European polymer journal
N2  - Chemical functionalization of poly(epsilon-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 M-w 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 T-g = - 60 to - 46 degrees 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.
KW  - copper-catalyzed alkyne-azide cycloaddition
KW  - chain-extended
KW  - polycaprolactone
KW  - RGD-peptide
KW  - side-chains functionalization
Y1  - 2020
U6  - https://doi.org/10.1016/j.eurpolymj.2020.109908
SN  - 0014-3057
SN  - 1873-1945
VL  - 136
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Naolou, Toufik
A1  - Lendlein, Andreas
A1  - Neffe, Axel T.
T1  - Amides as non-polymerizable catalytic adjuncts enable the ring-opening polymerization of lactide with ferrous acetate under mild conditions
JF  - Frontiers in Chemistry
N2  - 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 degrees C), associated with racemization. In the ROP of ester and amide group containing morpholinediones with Fe(OAc)(2) to polydepsipeptides at 135 degrees 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 degrees C, in the presence of N-ethylacetamide or N-rnethylbenzamide 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 degrees 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.
KW  - ring-opening polymerization
KW  - polyester
KW  - catalyst
KW  - iron
KW  - amide ligand
Y1  - 2019
U6  - https://doi.org/10.3389/fchem.2019.00346
SN  - 2296-2646
VL  - 7
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Tronci, Giuseppe
A1  - Neffe, Axel T.
A1  - Pierce, Benjamin Franklin
A1  - Lendlein, Andreas
T1  - An entropy-elastic gelatin-based hydrogel system
N2  - 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.
Y1  - 2010
UR  - http://www.rsc.org/Publishing/Journals/jm/index.asp
U6  - https://doi.org/10.1039/C0jm00883d
SN  - 0959-9428
ER  - 
TY  - JOUR
A1  - von Rüsten-Lange, Maik
A1  - Luetzow, Karola
A1  - Neffe, Axel T.
A1  - Lendlein, Andreas
T1  - Characterization of oligo(ethylene glycol) and oligoglycerol functionalized poly(ether imide) by angle-dependent X-ray photoelectron spectroscopy
JF  - Journal of applied biomaterials & functional materials
N2  - 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 alpha-amino-methoxy oligo(ethylene glycol) (M-n = 1,320 g.mol(-1)) or linear, side chain methylated monoamine oligoglycerols (M-n = 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.
KW  - Poly(ether imide)
KW  - Oligo(ethylene glycol)
KW  - Oligoglycerols
KW  - Angle-dependent X-ray induced photoelectron spectroscopy
KW  - Surface functionalization
Y1  - 2012
U6  - https://doi.org/10.5301/JABFM.2012.10345
SN  - 2280-8000
VL  - 10
IS  - 3
SP  - 215
EP  - 222
PB  - Wichtig
CY  - Milano
ER  - 
TY  - JOUR
A1  - Hauser, Sandra
A1  - Wodtke, Robert
A1  - Tondera, Christoph
A1  - Wodtke, Johanna
A1  - Neffe, Axel T.
A1  - Hampe, Jochen
A1  - Lendlein, Andreas
A1  - Löser, Reik
A1  - Pietzsch, Jens
T1  - Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials
JF  - ACS biomaterials science & engineering
N2  - 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.
KW  - extracellular matrix modifying enzymes
KW  - gelatin-based hydrogels
KW  - biomaterial-tissue interface
KW  - polyamines
KW  - optical imaging
Y1  - 2019
U6  - https://doi.org/10.1021/acsbiomaterials.9b01299
SN  - 2373-9878
VL  - 5
IS  - 11
SP  - 5979
EP  - 5989
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Vukicevic, Radovan
A1  - Neffe, Axel T.
A1  - Luetzow, Karola
A1  - Pierce, Benjamin F.
A1  - Lendlein, Andreas
T1  - Conditional Ultrasound Sensitivity of Poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] Microgels for Controlled Lipase Release
JF  - Macromolecular rapid communications
N2  - Triggering the release of cargo from a polymer network by ultrasonication as an external, non-invasive 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 degrees 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.
KW  - ultrasound
KW  - polymers
KW  - microgels
KW  - lipase release
KW  - controlled release
KW  - thermoresponsive polymers
KW  - biomaterials
Y1  - 2015
U6  - https://doi.org/10.1002/marc.201500311
SN  - 1022-1336
SN  - 1521-3927
VL  - 36
IS  - 21
SP  - 1891
EP  - 1896
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Federico, Stefania
A1  - Pierce, Benjamin F.
A1  - Piluso, Susanna
A1  - Wischke, Christian
A1  - Lendlein, Andreas
A1  - Neffe, Axel T.
T1  - Design of Decorin-Based Peptides That Bind to CollagenI and their Potential as Adhesion Moieties in Biomaterials
JF  - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition
N2  - Mimicking the binding epitopes of protein-protein interactions by using small peptides is important for generating modular biomimetic systems. A strategy is described for the design of such bioactive peptides without accessible structural data for the targeted interaction, and the effect of incorporating such adhesion peptides in complex biomaterial systems is demonstrated. The highly repetitive structure of decorin was analyzed to identify peptides that are representative of the inner and outer surface, and it was shown that only peptides based on the inner surface of decorin bind to collagen. The peptide with the highest binding affinity for collagenI, LHERHLNNN, served to slow down the diffusion of a conjugated dye in a collagen gel, while its dimer could physically crosslink collagen, thereby enhancing the elastic modulus of the gel by one order of magnitude. These results show the potential of the identified peptides for the design of biomaterials for applications in regenerative medicine.
KW  - biomaterials
KW  - collagen
KW  - gels
KW  - peptides
KW  - protein-protein interactions
Y1  - 2015
U6  - https://doi.org/10.1002/anie.201505227
SN  - 1433-7851
SN  - 1521-3773
VL  - 54
IS  - 37
SP  - 10980
EP  - 10984
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Piluso, Susanna
A1  - Lendlein, Andreas
A1  - Neffe, Axel T.
T1  - Enzymatic action as switch of bulk to surface degradation of clicked gelatin-based networks
JF  - Polymers for advanced technologies
N2  - 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 (>7nm) was in all cases larger than the hydrodynamic radius of the enzyme (4.5nm) 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. Copyright (c) 2016 John Wiley & Sons, Ltd.
KW  - Hydrogel
KW  - Biopolymer
KW  - Degradation
Y1  - 2017
U6  - https://doi.org/10.1002/pat.3962
SN  - 1042-7147
SN  - 1099-1581
VL  - 28
SP  - 1318
EP  - 1324
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Lau, Skadi
A1  - Liu, Yue
A1  - Maier, Anna
A1  - Braune, Steffen
A1  - Gossen, Manfred
A1  - Neffe, Axel T.
A1  - Lendlein, Andreas
T1  - Establishment of an in vitro thrombogenicity test system with cyclic olefin copolymer substrate for endothelial layer formation
JF  - MRS communications / a publication of the Materials Research Society
N2  - 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.
Y1  - 2021
U6  - https://doi.org/10.1557/s43579-021-00072-6
SN  - 2159-6867
VL  - 11
IS  - 5
SP  - 559
EP  - 567
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Neffe, Axel T.
A1  - Zhang, Quanchao
A1  - Hommes-Schattmann, Paul J.
A1  - Lendlein, Andreas
T1  - Ethylene oxide sterilization of electrospun poly(L-lactide)/poly(D-lactide) core/shell nanofibers
JF  - MRS advances
N2  - 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 degrees 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 (similar to 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 degrees C. No changes were detected in H-1-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.
Y1  - 2021
U6  - https://doi.org/10.1557/s43580-021-00058-5
SN  - 2059-8521
VL  - 6
IS  - 33
SP  - 786
EP  - 789
PB  - Springer
CY  - Cham
ER  - 
TY  - JOUR
A1  - Neffe, Axel T.
A1  - Loebus, Axel
A1  - Zaupa, Alessandro
A1  - Stötzel, Christian
A1  - Müller, Frank A.
A1  - Lendlein, Andreas
T1  - Gelatin functionalization with tyrosine derived moieties to increase the interaction with hydroxyapatite fillers
JF  - Acta biomaterialia
N2  - 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 ratios than those of the pure matrices. Shifts of the infra-red (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 cross-links 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 strengths (from 57 kPa up to 1.1 MPa) compared with the matrix polymers without affecting the elongation at break. Furthermore, an increased thermal stability of the networks from 40 to 85 degrees C could be demonstrated. The differences in the behaviour of the functionalized gelatins compared with pure gelatin as a matrix suggested an additional stabilizing bond between the incorporated aromatic groups and the HAp as supported by the IR results. The composites can potentially be applied as bone fillers.
KW  - Gelatin
KW  - Hydroxyapatite
KW  - Composite
KW  - Hydrogel
KW  - Biomaterial
Y1  - 2011
U6  - https://doi.org/10.1016/j.actbio.2010.11.025
SN  - 1742-7061
VL  - 7
IS  - 4
SP  - 1693
EP  - 1701
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Neffe, Axel T.
A1  - Lendlein, Andreas
T1  - Going Beyond Compromises in Multifunctionality of Biomaterials
JF  - Advanced healthcare materials
Y1  - 2015
U6  - https://doi.org/10.1002/adhm.201400724
SN  - 2192-2640
SN  - 2192-2659
VL  - 4
IS  - 5
SP  - 642
EP  - 645
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Piluso, Susanna
A1  - Hiebl, Bernhard
A1  - Gorb, Stanislav N.
A1  - Kovalev, Alexander
A1  - Lendlein, Andreas
A1  - Neffe, Axel T.
T1  - Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties
JF  - The international journal of artificial organs
N2  - 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.
KW  - Biomaterial
KW  - Hydrogel
KW  - Hyaluronic acid
KW  - Microindentation
KW  - Rheology
Y1  - 2011
U6  - https://doi.org/10.5301/IJAO.2011.6394
SN  - 0391-3988
VL  - 34
IS  - 2
SP  - 192
EP  - 197
PB  - Wichtig
CY  - Milano
ER  - 
TY  - JOUR
A1  - Neffe, Axel T.
A1  - Löwenberg, Candy
A1  - Lendlein, Andreas
T1  - Hydrogel networks by aliphatic dithiol Michael addition to glycidylmethacrylated gelatin
JF  - MRS advances : a journal of the Materials Research Society (MRS)
N2  - 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 H-1 NMR and FT-IR spectroscopy. Hydrogel swelling (460-1900 vol%) and mechanical properties (Young's modulus E = 59-512 kPa, elongation at break epsilon(b) = 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 degrees 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.
Y1  - 2021
U6  - https://doi.org/10.1557/s43580-021-00136-8
SN  - 2059-8521
VL  - 6
IS  - 33
SP  - 796
EP  - 800
PB  - Springer Nature Switzerland AG
CY  - Cham
ER  - 
TY  - JOUR
A1  - Tung, Wing Tai
A1  - Maring, Janita A.
A1  - Xu, Xun
A1  - Liu, Yue
A1  - Becker, Matthias
A1  - Somesh, Dipthi Bachamanda
A1  - Klose, Kristin
A1  - Wang, Weiwei
A1  - Sun, Xianlei
A1  - Ullah, Imran
A1  - Kratz, Karl
A1  - Neffe, Axel T.
A1  - Stamm, Christof
A1  - Ma, Nan
A1  - Lendlein, Andreas
T1  - In vivo performance of a cell and factor free multifunctional fiber mesh modulating postinfarct myocardial remodeling
JF  - Advanced Functional Materials
N2  - 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 mu m vs 400-600 mu m), 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.
KW  - bioinstructive materials
KW  - cardiac regeneration
KW  - function by structure;
KW  - modulation of in vivo regeneration
KW  - multifunctional biomaterials
Y1  - 2022
U6  - https://doi.org/10.1002/adfm.202110179
SN  - 1616-301X
SN  - 1616-3028
VL  - 32
IS  - 31
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Naolou, Toufik
A1  - Lendlein, Andreas
A1  - Neffe, Axel T.
T1  - Influence of metal softness on the metal-organic catalyzed polymerization of inorpholin-2,5-diones to oligodepsipeptides
JF  - European polymer journal
Y1  - 2016
U6  - https://doi.org/10.1016/j.eurpolymj.2016.10.011
SN  - 0014-3057
SN  - 1873-1945
VL  - 85
SP  - 139
EP  - 149
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Brunacci, Nadia
A1  - Wischke, Christian
A1  - Naolou, Toufik
A1  - Neffe, Axel T.
A1  - Lendlein, Andreas
T1  - Influence of surfactants on depsipeptide submicron particle formation
JF  - European Journal of Pharmaceutics and Biopharmaceutics
N2  - 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 M-n= 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-alpha-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. (C) 2016 Elsevier B.V. All rights reserved.
KW  - Depsipeptide
KW  - Particle size
KW  - Surfactants
KW  - Submicron particles
Y1  - 2017
U6  - https://doi.org/10.1016/j.ejpb.2016.11.011
SN  - 0939-6411
SN  - 1873-3441
VL  - 116
SP  - 61
EP  - 65
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Zaupa, Alessandro
A1  - Neffe, Axel T.
A1  - Pierce, Benjamin F.
A1  - Nöchel, Ulrich
A1  - Lendlein, Andreas
T1  - Influence of tyrosine-derived moieties and drying conditions on the formation of helices in gelatin
JF  - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences
N2  - 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 > T-c, called nu(short)) generally resulted in gelatins with relatively lower triple helical content (X-c,X-t = 1-2%) than lower temperature drying (T < T-c, called nu(long)) (X-c,X-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 nu(long) and E = 120-700 kPa for samples treated by nu(short)). 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.
Y1  - 2011
U6  - https://doi.org/10.1021/bm101029k
SN  - 1525-7797
VL  - 12
IS  - 1
SP  - 75
EP  - 81
PB  - American Chemical Society
CY  - Washington
ER  -