TY - JOUR A1 - Machatschek, Rainhard Gabriel A1 - Schöne, Anne-Christin A1 - Raschdorf, Elisa A1 - Ihlenburg, Ramona A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Interfacial properties of morpholine-2,5-dione-based oligodepsipeptides and multiblock copolymers JF - MRS Communications N2 - Oligodepsipeptides (ODPs) with alternating amide and ester bonds prepared by ring-opening polymerization of morpholine-2,5-dione derivatives are promising matrices for drug delivery systems and building blocks for multifunctional biomaterials. Here, we elucidate the behavior of three telechelic ODPs and one multiblock copolymer containing ODP blocks at the air-water interface. Surprisingly, whereas the oligomers and multiblock copolymers crystallize in bulk, no crystallization is observed at the air-water interface. Furthermore, polarization modulation infrared reflection absorption spectroscopy is used to elucidate hydrogen bonding and secondary structures in ODP monolayers. The results will direct the development of the next ODP-based biomaterial generation with tailored properties for highly sophisticated applications. Y1 - 2019 U6 - https://doi.org/10.1557/mrc.2019.21 SN - 2159-6859 SN - 2159-6867 VL - 9 IS - 1 SP - 170 EP - 180 PB - Cambridge Univ. Press CY - New York ER - TY - GEN A1 - Machatschek, Rainhard Gabriel A1 - Schöne, Anne-Christin A1 - Raschdorf, Elisa A1 - Ihlenburg, Ramona A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Interfacial properties of morpholine-2,5-dione-based oligodepsipeptides and multiblock copolymers T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Oligodepsipeptides (ODPs) with alternating amide and ester bonds prepared by ring-opening polymerization of morpholine-2,5-dione derivatives are promising matrices for drug delivery systems and building blocks for multifunctional biomaterials. Here, we elucidate the behavior of three telechelic ODPs and one multiblock copolymer containing ODP blocks at the air-water interface. Surprisingly, whereas the oligomers and multiblock copolymers crystallize in bulk, no crystallization is observed at the air-water interface. Furthermore, polarization modulation infrared reflection absorption spectroscopy is used to elucidate hydrogen bonding and secondary structures in ODP monolayers. The results will direct the development of the next ODP-based biomaterial generation with tailored properties for highly sophisticated applications. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1106 KW - block-copolymer KW - enzymatic degradation KW - poly(ester amide)s KW - controlled-release KW - films KW - nanocarriers Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-469755 SN - 1866-8372 IS - 1106 SP - 170 EP - 180 ER - TY - JOUR A1 - Piluso, Susanna A1 - Vukicevie, Radovan A1 - Nöchel, Ulrich A1 - Braune, Steffen A1 - Lendlein, Andreas A1 - Neffe, Axel T. T1 - Sequential alkyne-azide cycloadditions for functionalized gelatin hydrogel formation JF - European polymer journal N2 - 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. KW - Click chemistry KW - Hydrogel KW - Polymer functionalization KW - Biopolymer KW - Rheology KW - Multifunctionality Y1 - 2018 U6 - https://doi.org/10.1016/j.eurpolymj.2018.01.017 SN - 0014-3057 SN - 1873-1945 VL - 100 SP - 77 EP - 85 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Lützow, Karola A1 - Hommes-Schattmann, Paul J. A1 - Neffe, Axel T. A1 - Ahmad, Bilal A1 - Williams, Gareth R. A1 - Lendlein, Andreas T1 - Perfluorophenyl azide functionalization of electrospun poly(para-dioxanone) JF - Polymers for advanced technologies N2 - 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. KW - biological applications of polymers KW - fibers KW - functionalization of polymers KW - microstructure Y1 - 2018 U6 - https://doi.org/10.1002/pat.4331 SN - 1042-7147 SN - 1099-1581 VL - 30 IS - 5 SP - 1165 EP - 1172 PB - Wiley CY - Hoboken 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 - 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 - Zhang, Pengfei A1 - Rešetič, Andraž A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Multifunctionality in polymer networks by dynamic of coordination bonds JF - Macromolecular chemistry and physics N2 - The need for multifunctional materials is driven by emerging technologies and innovations, such as in the field of soft robotics and tactile or haptic systems, where minimizing the number of operational components is not only desirable, but can also be essential for realizing such devices. This study report on designing a multifunctional soft polymer material that can address a number of operating requirements such as solvent resistance, reshaping ability, self-healing capability, fluorescence stimuli-responsivity, and anisotropic structural functions. The numerous functional abilities are associated to rhodium(I)-phosphine coordination bonds, which in a polymer network act with their dynamic and non-covalently bonded nature as multifunctional crosslinks. Reversible aggregation of coordination bonds leads to changes in fluorescence emission intensity that responds to chemical or mechanical stimuli. The fast dynamics and diffusion of rhodium-phosphine ions across and through contacting areas of the material provide for reshaping and self-healing abilities that can be further exploited for assembly of multiple pieces into complex forms, all without any loss to material-sensing capabilities. KW - assembly capabilities KW - fluorescence stimuli‐ responsivity KW - multiple functions KW - reshaping abilities KW - rhodium(I)– phosphine KW - coordination bonds KW - solvent resistance Y1 - 2021 U6 - https://doi.org/10.1002/macp.202000394 SN - 1521-3935 VL - 222 IS - 3 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Sauter, Tilman A1 - Kratz, Karl A1 - Farhan, Muhammad A1 - Heuchel, Matthias A1 - Lendlein, Andreas T1 - Design and fabrication of fiber mesh actuators JF - Applied materials today N2 - Soft actuator performance can be tuned by chemistry or mechanical manipulation, but this adjustability is limited especially in view of their growing technological relevance. Inspired from textile engineering, we designed and fabricated fiber mesh actuators and introduced new features like anisotropic behavior and soft-tissue like elastic deformability. Design criteria for the meshes are the formation of fiber bundles, the angle between fiber bundles in different stacked layers and covalent crosslinks forming within and between fibers at their interfacial contact areas. Through crosslinking the interfiber bond strength increased from a bond transmitting neither axial nor rotational loads (pin joint) to a bond strength capable of both (welded joint). For non-linear elastic stiffening, stacked fiber bundles with four embracing fibers were created forming microstructural rhombus shapes. Loading the rhombus diagonally allowed generation of “soft tissue”-like mechanics. By adjustment of stacking angles, the point of strong increase in stress is tuned. While the highest stresses are observed in aligned and crosslinked fiber mats along the direction of the fiber, the strongest shape-memory actuation behavior is found in randomly oriented fiber mats. Fiber mesh actuators controlled by temperature are of high significance as soft robot skins and as for active patches supporting tissue regeneration. Y1 - 2022 U6 - https://doi.org/10.1016/j.apmt.2022.101562 SN - 2352-9407 VL - 29 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Tartivel, Lucile A1 - Blocki, Anna M. A1 - Braune, Steffen A1 - Jung, Friedrich A1 - Behl, Marc A1 - Lendlein, Andreas T1 - An Inverse shape-memory hydrogel scaffold switching upon cooling in a tissue-tolerated temperature range JF - Advanced materials interfaces N2 - Tissue reconstruction has an unmet need for soft active scaffolds that enable gentle loading with regeneration-directing bioactive components by soaking up but also provide macroscopic dimensional stability. Here microporous hydrogels capable of an inverse shape-memory effect (iSME) are described, which in contrast to classical shape-memory polymers (SMPs) recover their permanent shape upon cooling. These hydrogels are designed as covalently photo cross-linked polymer networks with oligo(ethylene glycol)-oligo(propylene glycol)-oligo(ethylene glycol) (OEG-OPG-OEG) segments. When heated after deformation, the OEG-OPG-OEG segments form micelles fixing the temporary shape. Upon cooling, the micelles dissociate again, the deformation is reversed and the permanent shape is obtained. Applicability of this iSME is demonstrated by the gentle loading of platelet-rich plasma (PRP) without causing any platelet activation during this process. PRP is highly bioactive and is widely acknowledged for its regenerative effects. Hence, the microporous inverse shape-memory hydrogel (iSMH) with a cooling induced pore-size effect represents a promising candidate scaffold for tissue regeneration for potential usage in minimally invasive surgery applications. KW - active scaffold KW - critical micellation temperature KW - hydrogel KW - inverse KW - shape-memory effect KW - platelet-rich plasma Y1 - 2022 U6 - https://doi.org/10.1002/admi.202101588 SN - 2196-7350 VL - 9 IS - 6 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Machatschek, Rainhard Gabriel A1 - Heuchel, Matthias A1 - Lendlein, Andreas T1 - Hydrolytic stability of polyetherimide investigated in ultrathin films JF - Journal of materials research : JMR / Materials Research Society N2 - Increasing the surface hydrophilicity of polyetherimide (PEI) through partial hydrolysis of the imide groups while maintaining the length of the main-chain was explored for adjusting its function in biomedical and membrane applications. The outcome of the polymer analogous reaction, i.e., the degree of ring opening and chain cleavage, is difficult to address in bulk and microstructured systems, as these changes only occur at the interface. Here, the reaction was studied at the air-water interface using the Langmuir technique, assisted by atomic force microscopy and vibrational spectroscopy. Slow PEI hydrolysis sets in at pH > 12. At pH = 14, the ring opening is nearly instantaneous. Reduction of the layer viscosity with time at pH = 14 suggested moderate chain cleavage. No hydrolysis was observed at pH = 1. Hydrolyzed PEI films had a much more cohesive structure, suggesting that the nanoporous morphology of PEI can be tuned via hydrolysis. KW - 2D materials KW - Membrane KW - Polymer KW - Water KW - Nanostructure Y1 - 2021 U6 - https://doi.org/10.1557/s43578-021-00267-6 SN - 0884-2914 SN - 2044-5326 VL - 36 IS - 14 SP - 2987 EP - 2994 PB - Springer CY - Berlin ER - TY - JOUR A1 - Bochove, Bas van A1 - Grijpma, Dirk W. A1 - Lendlein, Andreas A1 - Seppälä, Jukka T1 - Designing advanced functional polymers for medicine JF - European polymer journal : EPJ Y1 - 2021 U6 - https://doi.org/10.1016/j.eurpolymj.2021.110573 SN - 0014-3057 VL - 155 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Folikumah, Makafui Yao A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Thiol-Thioester exchange reactions in precursors enable pH-triggered hydrogel formation JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - Bio-interactive hydrogel formation in situ requires sensory capabilities toward physiologically relevant stimuli. Here, we report on pH-controlled in situ hydrogel formation relying on latent cross-linkers, which transform from pH sensors to reactive molecules. In particular, thiopeptolide/thio-depsipeptides were capable of pH-sensitive thiol-thioester exchange reactions to yield a,co-dithiols, which react with maleimide-functionalized multi-arm polyethylene glycol to polymer networks. Their water solubility and diffusibility qualify thiol/thioester-containing peptide mimetics as sensory precursors to drive in situ localized hydrogel formation with potential applications in tissue regeneration such as treatment of inflamed tissues of the urinary tract. Y1 - 2021 U6 - https://doi.org/10.1021/acs.biomac.0c01690 SN - 1525-7797 SN - 1526-4602 VL - 22 IS - 5 SP - 1875 EP - 1884 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Neffe, Axel T. A1 - Löwenberg, Candy A1 - Julich-Gruner, Konstanze K. A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Thermally-induced shape-memory behavior of degradable gelatin-based networks JF - International journal of molecular sciences N2 - 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) alpha,omega-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 degrees C. The hydrogels were hydrolytically degradable, with full degradation to water-soluble products within one week at 37 degrees 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 R-r 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. KW - shape-memory hydrogel KW - active polymer KW - biopolymer KW - mechanical KW - properties KW - degradation Y1 - 2021 U6 - https://doi.org/10.3390/ijms22115892 SN - 1422-0067 SN - 1661-6596 VL - 22 IS - 11 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Julich-Gruner, Konstanze K. A1 - Löwenberg, Candy A1 - Neffe, Axel T. A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Recent trends in the chemistry of shape-memory polymers JF - Macromolecular chemistry and physics N2 - 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. KW - multifunctional polymers KW - networks KW - shape-memory polymers KW - stimuli-sensitive polymers KW - triple-shape effect Y1 - 2013 U6 - https://doi.org/10.1002/macp.201200607 SN - 1022-1352 VL - 214 IS - 5 SP - 527 EP - 536 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Federico, Stefania A1 - Nöchel, Ulrich A1 - Löwenberg, Candy A1 - Lendlein, Andreas A1 - Neffe, Axel T. T1 - Supramolecular hydrogel networks formed by molecular recognition of collagen and a peptide grafted to hyaluronic acid JF - Acta biomaterialia N2 - 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. Statement of Significance Biopolymers of the extracellular matrix (ECM) like collagen or hyaluronan are attractive starting materials for biomaterials. While in biomaterial science covalent crosslinking is often employed, in the native ECM, stabilization and macromolecular organization is primarily based on non-covalent interactions, which allows dynamic changes of the materials. Here, we show that collagen-binding peptides, derived from the small proteoglycan decorin, grafted to hyaluronic acid enable supramolecular stabilization of collagen hydrogels. These hydrogels have storage moduli more than one order of magnitude higher than mixtures of collagen and hyaluronic acid. Furthermore, the peptide supported the structural organization of collagen. Such hydrogels could be employed for a diverse range of applications in regenerative medicine. Furthermore, the rational design helps in the understanding ECM structuring. KW - Biopolymers KW - Collagen-binding peptide KW - Hyaluronic acid KW - Hydrogels KW - Mechanical properties Y1 - 2016 U6 - https://doi.org/10.1016/j.actbio.2016.04.018 SN - 1742-7061 SN - 1878-7568 VL - 38 SP - 1 EP - 10 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Blocki, Anna A1 - Löwenberg, Candy A1 - Jiang, Yi A1 - Kratz, Karl A1 - Neffe, Axel T. A1 - Jung, Friedrich A1 - Lendlein, Andreas T1 - Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties JF - Polymers for advanced technologies N2 - 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. Copyright (c) 2016 John Wiley & Sons, Ltd. KW - mechanotransduction KW - hydrogel KW - gelatin KW - cell encapsulation KW - matrix elasticity Y1 - 2017 U6 - https://doi.org/10.1002/pat.3947 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1245 EP - 1251 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - You, Zewang A1 - Behl, Marc A1 - Löwenberg, Candy A1 - Lendlein, Andreas T1 - pH-sensitivity and conformation change of the n-terminal methacrylated peptide VK20 JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - N-terminal methacrylation of peptide MAXI, which is capable of conformational changes variation of the pH, results in a peptide, named VK20. Increasing the reactivity of this terminal group enables further coupling reactions or chemical modifications of the peptidc. However, this end group functionalization may influence the ability of confonnational changes of VK20; as well as its properties. In this paper; the influence of pH on the transition between random coil and beta-sheet conformation of VK20; including the transition kinetics, were investigated. At pH values of 9 and higher, the kinetics beta-sheet formation increased tor VK(2 0, compared to MAXI. The self-assembly into beta-sheets recognized by the formation of a physically crosslinked gel was furthermore indicated by a significant increase of G. An increase in pH (from 9 to 9.5) led to a faster gelation of the peptide VK20. Simultaneously, G was increased from 460 +/- 70 Pa (at pH 9) to 1520 +/- 180 Pa (at pH 9.5). At the nanoscale, the gel showed a highly interconnected fibrillar/network structure with uniform fibril widths of approximately 3.4 +/- 0.5 nm (N=30). The recovery of the peptide conformation back to random coil resulted in the dissolution of the gel; whereby the kinetics of the recovery depended on the pH. Conclusively, the ability of MAXI to undergo confommtional changes was not affected by N-terminal methacrylation whereas the kinetics of pH-sensitive beta-sheet formations has been increased. Y1 - 2017 U6 - https://doi.org/10.1557/adv.2017.491 SN - 2059-8521 VL - 2 SP - 2571 EP - 2579 PB - Cambridge University Press CY - Cambridge ER - TY - JOUR A1 - Löwenberg, Candy A1 - Tripodo, Giuseppe A1 - Julich-Gruner, Konstanze K. A1 - Neffe, Axel T. A1 - Lendlein, Andreas T1 - Supramolecular gelatin networks based on inclusion complexes JF - Macromolecular bioscience N2 - 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 degrees 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. KW - cyclodextrin KW - gelatin KW - inclusion complex KW - supramolecular polymer network Y1 - 2020 U6 - https://doi.org/10.1002/mabi.202000221 SN - 1616-5187 SN - 1616-5195 VL - 20 IS - 10 PB - Wiley-VCH CY - Weinheim 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 -