TY - JOUR A1 - Schöne, Anne-Christin A1 - Kratz, Karl A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - The relevance of hydrophobic segments in multiblock copolyesterurethanes for their enzymatic degradation at the air-water interface JF - Polymer : the international journal for the science and technology of polymers N2 - The interplay of an enzyme with a multiblock copolymer PDLCL containing two segments of different hydrophilicity and degradability is explored in thin films at the air-water interface. The enzymatic degradation was studied in homogenous Langmuir monolayers, which are formed when containing more than 40 wt% oligo(epsilon-caprolactone) (OCL). Enzymatic degradation rates were significantly reduced with increasing content of hydrophobic oligo(omega-pentadecalactone) (OPDL). The apparent deceleration of the enzymatic process is caused by smaller portion of water-soluble degradation fragments formed from degradable OCL fragments. Beside the film degradation, a second competing process occurs after adding lipase from Pseudomonas cepacia into the subphase, namely the enrichment of the lipase molecules in the polymeric monolayer. The incorporation of the lipase into the Langmuir film is experimentally revealed by concurrent surface area enlargement and by Brewster angle microscopy (BAM). Aside from the ability to provide information about the degradation behavior of polymers, the Langmuir monolayer degradation (LMD) approach enables to investigate polymer-enzyme interactions for non-degradable polymers. (C) 2016 Elsevier Ltd. All rights reserved. KW - Multiblock copolymer KW - Enzymatic polymer degradation KW - Oligo(omega-pentadecalactone) KW - Oligo(epsilon-caprolactone) KW - Langmuir monolayer degradation technique Y1 - 2016 U6 - https://doi.org/10.1016/j.polymer.2016.09.001 SN - 0032-3861 SN - 1873-2291 VL - 102 SP - 92 EP - 98 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Schöne, Anne-Christin A1 - Kratz, Karl A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Polymer architecture versus chemical structure as adjusting tools for the enzymatic degradation of oligo(epsilon-caprolactone) based films at the air-water interface JF - Polymer Degradation and Stability N2 - The enzymatic degradation of oligo(epsilon-caprolactone) (OCL) based films at the air-water interface is investigated by Langmuir monolayer degradation (LMD) experiments to elucidate the influence of the molecular architecture and of the chemical structure on the chain scission process. For that purpose, the interactions of 2D monolayers of two star-shaped poly(epsilon-caprolactone)s (PCLs) and three linear OCL based copolyesterurethanes (P(OCL-U)) with the lipase from Pseudomonas cepacia are evaluated in comparison to linear OCL. While the architecture of star-shaped PCL Langmuir layers slightly influences their degradability compared to OCL films, significantly retarded degradations are observed for P(OCL-U) films containing urethane junction units derived from 2, 2 (4), 4-trimethyl hexamethylene diisocyanate (TMDI), hexamethylene diisocyanate (HDI) or lysine ethyl ester diisocyanate (LDI). The enzymatic degradation of the OCL based 2D structures is related to the presence of hydrophilic groups within the macromolecules rather than to the packing density of the film or to the molecular weight. The results reveal that the LMD technique allows the parallel analysis of both the film/enzyme interactions and the degradation process on the molecular level. (C) 2016 Elsevier Ltd. All rights reserved. KW - Langmuir technique KW - Oligo(epsilon-caprolactone) KW - Enzymatic degradation KW - Polymer architecture Y1 - 2016 U6 - https://doi.org/10.1016/j.polymdegradstab.2016.07.010 SN - 0141-3910 SN - 1873-2321 VL - 131 SP - 114 EP - 121 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Yan, Wan A1 - Fang, Liang A1 - Nöchel, Ulrich A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Influence of programming strain rates on the shape-memory performance of semicrystalline multiblock copolymers JF - Journal of polymer science : B, Polymer physics N2 - Multiblock copolymers named PCL-PIBMD consisting of crystallizable poly(epsilon-caprolactone) segments and crystallizable poly[oligo(3S-iso-butylmorpholine-2,5-dione)] segments coupled by trimethyl hexamethylene diisocyanate provide a versatile molecular architecture for achieving shape-memory effects (SMEs) in polymers. The mechanical properties as well as the SME performance of PCL-PIBMD can be tailored by the variation of physical parameters during programming such as deformation strain or applied temperature protocols. In this study, we explored the influence of applying different strain rates during programming on the resulting nanostructure of PCL-PIBMD. Programming was conducted at 50 degrees C by elongation to epsilon(m)=50% with strain rates of 1 or 10 or 50 mmmin(-1). The nanostructural changes were visualized by atomic force microscopy (AFM) measurements and investigated by in situ wide and small angle X-ray scattering experiments. With increasing the strain rate, a higher degree of orientation was observed in the amorphous domains. Simultaneously the strain-induced formation of new PIBMD crystals as well as the fragmentation of existing large PIBMD crystals occurred. The observed differences in shape fixity ratio and recovery stress of samples deformed with various strain rates can be attributed to their different nanostructures. The achieved findings can be relevant parameters for programming the shape-memory polymers with designed recovery forces. (c) 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1935-1943 KW - atomic force microscopy (AFM) KW - crystal structures KW - crystallization KW - multiblock copolymer KW - stimuli-sensitive polymers KW - SAXS KW - shape-memory effect KW - WAXS KW - X-ray scattering Y1 - 2016 U6 - https://doi.org/10.1002/polb.24097 SN - 0887-6266 SN - 1099-0488 VL - 54 SP - 1935 EP - 1943 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Braune, Steffen A1 - Gross, M. A1 - Walter, M. A1 - Zhou, Shengqiang A1 - Dietze, Siegfried A1 - Rutschow, S. A1 - Lendlein, Andreas A1 - Tschoepe, C. A1 - Jung, Friedrich T1 - Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials JF - Journal of biomedical materials research : an official journal of the Society for Biomaterials, the Japanese Society for Biomaterials; the Australian Society for Biomaterials N2 - On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet—indicating the spreading and activation of the platelets—was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials. KW - platelets KW - biomaterials KW - hemocompatibility KW - cardiovascular disease KW - cardiovascular implant Y1 - 2016 U6 - https://doi.org/10.1002/jbm.b.33366 SN - 1552-4973 SN - 1552-4981 VL - 104 SP - 210 EP - 217 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Braune, Steffen A1 - Froehlich, G. M. A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Effect of temperature on platelet adherence JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - BACKGROUND: Thrombogenicity is one of the main parameters tested in vitro to evaluate the hemocompatibility of artificial surfaces. While the influence of the temperature on platelet aggregation has been addressed by several studies, the temperature influence on the adherence of platelets to body foreign surfaces as an important aspect of biomedical device handling has not yet been explored. Therefore, we analyzed the influence of two typically applied incubation-temperatures (22 degrees C and 37 degrees C) on the adhesion of platelets to biomaterials. MATERIAL AND METHODS: Thrombogenicity of three different polymers - medical grade poly(dimethyl siloxane) (PDMS), polytetrafluoroethylene (PTFE) and polyethylene terephthalate (PET) - were studied in an in vitro static test. Platelet adhesion was studied with stringently characterized blood from apparently healthy subjects. Collection of whole blood and preparation of platelet rich plasma (PRP) was carried out at room temperature (22 degrees C). PRP was incubated with the polymers either at 22 degrees C or 37 degrees C. Surface adherent platelets were fixed, fluorescently labelled and assessed by an image-based approach. RESULTS AND DISCUSSION: Differences in the density of adherent platelets after incubation at 22 degrees C and 37 degrees C occurred on PDMS and PET. Similar levels of adherent platelets were observed on the very thrombogenic PTFE. The covered surface areas per single platelet were analyzed to measure the state of platelet activation and revealed no differences between the two incubation temperatures for any of the analyzed polymers. Irrespective of the observed differences between the low and medium thrombogenic PDMS and PET and the higher variability at 22 degrees C, the thrombogenicity of the three investigated polymers was evaluated being comparable at both incubation temperatures. KW - Biomaterial KW - thrombogenicity KW - platelet adhesion KW - platelet activation KW - temperature Y1 - 2016 U6 - https://doi.org/10.3233/CH-152028 SN - 1386-0291 SN - 1875-8622 VL - 61 SP - 681 EP - 688 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Bhaskar, Thanga Bhuvanesh Vijaya A1 - Ma, Nan A1 - Lendlein, Andreas A1 - Roch, Toralf T1 - The interaction of human macrophage subsets with silicone as a biomaterial JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Silicones are widely used as biomaterials for medical devices such as extracorporeal equipments. However, there is often conflicting evidence about their supposed cell-and histocompatibility. Macrophages could mediate silicone-induced adverse responses such as foreign body reaction and fibrous encapsulation. The polarization behaviour of macrophages could determine the clinical outcome after implantation of biomaterials. Induction of classically activated macrophages (CAM) may induce and support uncontrolled inflammatory responses and undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. This study compared the interaction of non-polarized macrophages (M0), CAM, and AAM with commercially available tissue culture polystyrene (TCP) and a medical grade silicone-based biomaterial, regarding the secretion of inflammatory mediators such as cytokines and chemokines. Firstly, by using the Limulus amoebocyte lysate (LAL) test the silicone films were shown to be free of soluble endotoxins, which is the prerequisite to investigate their interaction with primary immune cells. Primary human monocyte-derived macrophages (M0) were polarized into CAM and AAM by addition of suitable differentiation factors. These macrophage subsets were incubated on the materials for 24 hours and their viability and cytokine secretion was assessed. In comparison to TCP, cell adhesion was lower on silicone after 24 hours for all three macrophage subsets. However, compared to TCP, silicone induced higher levels of certain inflammatory and chemotactic cytokines in M0, CAM, and AAM macrophage subsets. Conclusively, it was shown that silicone has the ability to induce a pro-inflammatory state to different magnitudes dependent on the macrophage subsets. This priming of the macrophage phenotype by silicone could explain the incidence of severe foreign body complications observed in vivo. KW - Biomaterials KW - silicone KW - macrophage subsets KW - cytokines/chemokines Y1 - 2015 U6 - https://doi.org/10.3233/CH-151991 SN - 1386-0291 SN - 1875-8622 VL - 61 IS - 2 SP - 119 EP - 133 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Roch, Toralf A1 - Kratz, Karl A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Polymeric inserts differing in their chemical composition as substrates for dendritic cell cultivation JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Dendritic cells (DC) contribute to immunity by presenting antigens to T cells and shape the immune response by the secretion of cytokines. Due to their immune stimulatory potential DC-based therapies are promising approaches to overcome tolerance e.g. against tumors. In order to enforce the immunogenicity of DCs, they have to be matured and activated in vitro, which requires an appropriate cell culture substrate, supporting their survival expansion and activation. Since most cell culture devices are not optimized for DC growth, it is hypothesized that polymers with certain physicochemical properties can positively influence the DC cultures. With the aim to evaluate the effects that polymers with different chemical compositions have on the survival, the activation status, and the cytokine/chemokine secretion profile of DC, their interaction with polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI), and poly(styrene-co-acrylonitrile) (PSAN)-based cell culture inserts was investigated. By using this insert system, which fits exactly into 24 well cell culture plates, effects induced from the culture dish material can be excluded. The viability of untreated DC after incubation with the different inserts was not influenced by the different inserts, whereas LPS-activatedDCshowed an increased survival after cultivation on PC, PS, and PSAN compared to tissue culture polystyrene (TCP). The activation status of DC estimated by the expression of CD40, CD80, CD83, CD86 and HLA-DR expression was not altered by the different inserts in untreated DC but slightly reduced when LPS-activated DC were cultivated on PC, PS, PSAN, and PEI compared to TCP. For each polymeric cell culture insert a distinct cytokine profile could be observed. Since inserts with different chemical compositions of the inserts did not substantially alter the behavior of DC all insert systems could be considered as alternative substrate. The observed increased survival on some polymers, which showed in contrast to TCP a hydrophobic surface, could be beneficial for certain applications such as T cell expansion and activation. KW - Biomaterials KW - dendritic cells KW - cell culture device KW - amorphous polymers Y1 - 2015 U6 - https://doi.org/10.3233/CH-152004 SN - 1386-0291 SN - 1875-8622 VL - 61 IS - 2 SP - 347 EP - 357 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Schöne, Anne-Christin A1 - Roch, Toralf A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer techniques JF - Interface : journal of the Royal Society N2 - Polymeric biomaterials are of specific relevance in medical and pharmaceutical applications due to their wide range of tailorable properties and functionalities. The knowledge about interactions of biomaterials with their biological environment is of crucial importance for developing highly sophisticated medical devices. To achieve optimal in vivo performance, a description at the molecular level is required to gain better understanding about the surface of synthetic materials for tailoring their properties. This is still challenging and requires the comprehensive characterization of morphological structures, polymer chain arrangements and degradation behaviour. The review discusses selected aspects for evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer methods as powerful techniques for studying interfacial properties, such as morphological and degradation processes. The combination of spectroscopic, microscopic and scattering methods with the Langmuir techniques adapted to polymers can substantially improve the understanding of their in vivo behaviour. KW - Langmuir monolayer KW - biodegradable polymers KW - air - water interface KW - protein Langmuir layers Y1 - 2017 U6 - https://doi.org/10.1098/rsif.2016.1028 SN - 1742-5689 SN - 1742-5662 VL - 14 PB - Royal Society CY - London ER - TY - JOUR A1 - Balk, Maria A1 - Behl, Marc A1 - Nöchel, Ulrich A1 - Lendlein, Andreas T1 - Enzymatically triggered Jack-in-the-box-like hydrogels JF - ACS applied materials & interfaces / American Chemical Society N2 - Enzymes can support the synthesis or degradation of biomacromolecules in natural processes. Here, we demonstrate that enzymes can induce a macroscopic-directed movement of microstructured hydrogels following a mechanism that we call a "Jack-in-the-box" effect. The material's design is based on the formation of internal stresses induced by a deformation load on an architectured microscale, which are kinetically frozen by the generation of polyester locking domains, similar to a Jack-in-thebox toy (i.e., a compressed spring stabilized by a closed box lid). To induce the controlled macroscopic movement, the locking domains are equipped with enzyme-specific cleavable bonds (i.e., a box with a lock and key system). As a result of enzymatic reaction, a transformed shape is achieved by the release of internal stresses. There is an increase in entropy in combination with a swelling-supported stretching of polymer chains within the microarchitectured hydrogel (i.e., the encased clown pops-up with a pre-stressed movement when the box is unlocked). This utilization of an enzyme as a physiological stimulus may offer new approaches to create interactive and enzyme-specific materials for different applications such as an optical indicator of the enzyme's presence or actuators and sensors in biotechnology and in fermentation processes. KW - enzyme KW - hydrogels KW - stimuli-sensitive materials KW - shape change KW - poly(e-caprolactone) KW - switch KW - microporous Y1 - 2021 U6 - https://doi.org/10.1021/acsami.1c00466 SN - 1944-8244 SN - 1944-8252 VL - 13 IS - 7 SP - 8095 EP - 8101 PB - American Chemical Society CY - Washington, DC ER - TY - JOUR A1 - Frieß, Fabian A1 - Lendlein, Andreas A1 - Wischke, Christian T1 - Switching microobjects from low to high aspect ratios using a shape-memory effect JF - Soft matter N2 - Spherical particles from shape-memory polymers (SMP) can be stretched to ellipsoids with high aspect ratio (AR) and temporarily stabilized. They can switch back to low AR upon thermal stimulation. Here, the creation of an alternative shape-switching capability of particles from low to high AR is introduced, where a SMP matrix from polyvinyl alcohol (PVA) is used to create crosslinked high AR particles and to program the embedded micrometer-sized particles from a second SMP (oligo(epsilon-caprolactone) micronetworks, MN) with a low switching temperature T-sw. This programming proceeds through shape-recovery of the PVA matrix, from which the MN are harvested by PVA matrix dissolution. The use of a dissolvable SMP matrix may be a general strategy to efficiently create systems with complex moving capabilities. Y1 - 2021 U6 - https://doi.org/10.1039/d1sm00947h SN - 1744-6848 VL - 17 IS - 41 SP - 9326 EP - 9331 PB - Royal Society of Chemistry CY - London ER - TY - INPR A1 - Julich-Gruner, Konstanze K. A1 - Pandit, Abhay A1 - Lendlein, Andreas T1 - Advanced Functional Polymers Addressing the Needs of Modern Medicine T2 - Macromolecular rapid communications Y1 - 2015 U6 - https://doi.org/10.1002/marc.201500575 SN - 1022-1336 SN - 1521-3927 VL - 36 IS - 21 SP - 1859 EP - 1861 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Lau, Skadi A1 - Gossen, Manfred A1 - Lendlein, Andreas T1 - Designing cardiovascular implants taking in view the endothelial basement membrane JF - International journal of molecular sciences N2 - Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure-function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field. KW - endothelial cells KW - bioinstructive implants KW - vascular grafts KW - tissue KW - engineering KW - bioprinting KW - bioinspired materials KW - biological membrane KW - endothelial basement membrane KW - biomaterial Y1 - 2021 U6 - https://doi.org/10.3390/ijms222313120 SN - 1422-0067 VL - 22 IS - 23 PB - MDPI CY - Basel ER - TY - JOUR A1 - Machatschek, Rainhard Gabriel A1 - Heuchel, Matthias A1 - Lendlein, Andreas T1 - Thin-layer studies on surface functionalization of polyetherimide BT - hydrolysis versus amidation JF - Journal of materials research : JMR / Materials Research Society N2 - Among the high-performance and engineering polymers, polyimides and the closely related polyetherimide (PEI) stand out by their capability to react with nucleophiles under relatively mild conditions. By targeting the phthalimide groups in the chain backbone, post-functionalization offers a pathway to adjust surface properties such as hydrophilicity, solvent resistance, and porosity. Here, we use ultrathin PEI films on a Langmuir trough as a model system to investigate the surface functionalization with ethylene diamine and tetrakis(4-aminophenyl)porphyrin as multivalent nucleophiles. By means of AFM, Raman spectroscopy, and interfacial rheology, we show that hydrolysis enhances the chemical and mechanical stability of ultrathin films and allows for the formation of EDC/NHS-activated esters. Direct amidation of PEI was achieved in the presence of a Lewis acid catalyst, resulting in free amine groups rather than cross-linking. When comparing amidation with hydrolysis, we find a greater influence of the latter on material properties. KW - Membrane KW - Nanostructure KW - Polymer KW - Raman spectroscopy KW - Scanning probe microscopy (SPM) KW - Surface reaction KW - Thin film Y1 - 2021 U6 - https://doi.org/10.1557/s43578-021-00339-7 SN - 0884-2914 SN - 2044-5326 VL - 37 IS - 1 SP - 67 EP - 76 PB - Springer CY - Berlin ER - TY - JOUR A1 - Machatschek, Rainhard Gabriel A1 - Lendlein, Andreas T1 - Fundamental insights in PLGA degradation from thin film studies JF - Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems N2 - Poly(lactide-co-glycolide)s are commercially available degradable implant materials, which are typically selected based on specifications given by the manufacturer, one of which is their molecular weight. Here, we address the question whether variations in the chain length and their distribution affect the degradation behavior of Poly[(rac-lactide)-co-glycolide]s (PDLLGA). The hydrolysis was studied in ultrathin films at the air-water interface in order to rule out any morphological effects. We found that both for purely hydrolytic degradation as well as under enzymatic catalysis, the molecular weight has very little effect on the overall degradation kinetics of PDLLGAs. The quantitative analysis suggested a random scission mechanism. The monolayer experiments showed that an acidic micro-pH does not accelerate the degradation of PDLLGAs, in contrast to alkaline conditions. The degradation experiments were combined with interfacial rheology measurements, which showed a drastic decrease of the viscosity at little mass loss. The extrapolated molecular weight behaved similar to the viscosity, dropping to a value near to the solubility limit of PDLLGA oligomers before mass loss set in. This observation suggests a solubility controlled degradation of PDLLGA. Conclusively, the molecular weight affects the degradation of PDLLGA devices mostly in indirect ways, e.g. by determining their morphology and porosity during fabrication. Our study demonstrates the relevance of the presented Langmuir degradation method for the design of controlled release systems. KW - PDLLGA KW - Degradation KW - Langmuir monolayer Y1 - 2019 U6 - https://doi.org/10.1016/j.jconrel.2019.12.044 SN - 0168-3659 SN - 1873-4995 VL - 319 SP - 276 EP - 284 PB - Elsevier CY - New York ER - TY - JOUR A1 - Wang, Weiwei A1 - Naolou, Toufik A1 - Ma, Nan A1 - Deng, Zijun A1 - Xu, Xun A1 - Mansfeld, Ulrich A1 - Wischke, Christian A1 - Gossen, Manfred A1 - Neffe, Axel T. A1 - Lendlein, Andreas T1 - Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - 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 M (n) similar to 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. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biomac.7b01034 SN - 1525-7797 SN - 1526-4602 VL - 18 SP - 3819 EP - 3833 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Hommes-Schattmann, Paul J. A1 - Neffe, Axel T. A1 - Ahmad, Bilal A1 - Williams, Gareth R. A1 - Vanneaux, Valerie A1 - Menasche, Philippe A1 - Kalfa, David A1 - Lendlein, Andreas T1 - RGD constructs with physical anchor groups as polymer co-electrospinnable cell adhesives JF - Polymers for advanced technologies N2 - 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. Copyright (c) 2016 John Wiley & Sons, Ltd. KW - electrospinning KW - RGD peptides KW - cell adhesion KW - biofunctionalization Y1 - 2017 U6 - https://doi.org/10.1002/pat.3963 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1312 EP - 1317 PB - Wiley CY - Hoboken 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 - 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 - 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 - 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 - 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 - 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 - Lange, Maik A1 - Braune, Steffen A1 - Luetzow, Karola A1 - Richau, Klaus A1 - Scharnagl, Nico A1 - Weinhart, Marie A1 - Neffe, Axel T. A1 - Jung, Friedrich A1 - Haag, Rainer A1 - Lendlein, Andreas T1 - Surface functionalization of poly(ether imide) membranes with linear, methylated oligoglycerols for reducing thrombogenicity JF - Macromolecular rapid communications N2 - 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. KW - hemocompatibility KW - poly(ethylene glycol) KW - polyglycerol KW - polyimides KW - surface chemistry Y1 - 2012 U6 - https://doi.org/10.1002/marc.201200426 SN - 1022-1336 VL - 33 IS - 17 SP - 1487 EP - 1492 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Neffe, Axel T. A1 - von Rüsten-Lange, Maik A1 - Braune, Steffen A1 - Lützow, Karola A1 - Roch, Toralf A1 - Richau, Klaus A1 - Jung, Friedrich A1 - Lendlein, Andreas T1 - Poly(ethylene glycol) grafting to Poly(ether imide) membranes - influence on protein adsorption and Thrombocyte adhesion JF - Macromolecular bioscience N2 - 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 (M-n=1kDa or 10kDa) 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. KW - biomaterials KW - poly(ethylene glycol) KW - protein adsorption KW - surface functionalization KW - thrombocyte adhesion Y1 - 2013 U6 - https://doi.org/10.1002/mabi.201300309 SN - 1616-5187 SN - 1616-5195 VL - 13 IS - 12 SP - 1720 EP - 1729 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 - 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 - 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 - INPR A1 - Lendlein, Andreas A1 - Neffe, Axel T. A1 - Jerome, Christine T1 - Advanced functional polymers for medicine T2 - Advanced healthcare materials Y1 - 2014 U6 - https://doi.org/10.1002/adhm.201400718 SN - 2192-2640 SN - 2192-2659 VL - 3 IS - 12 SP - 1939 EP - 1940 PB - Wiley-Blackwell CY - Hoboken ER - TY - CHAP A1 - Neffe, Axel T. A1 - Zaupa, Alessandro A1 - Lendlein, Andreas T1 - Physical crosslinking of gelatin a supramolecular approach tobiomaterial T2 - The international journal of artificial organs Y1 - 2011 SN - 0391-3988 VL - 34 IS - 8 SP - 656 EP - 656 PB - Wichtig CY - Milano ER - TY - JOUR A1 - Sarem, Melika A1 - Arya, Neha A1 - Heizmann, Miriam A1 - Neffe, Axel T. A1 - Barbero, Andrea A1 - Gebauer, Tim P. A1 - Martin, Ivan A1 - Lendlein, Andreas A1 - Shastri, V. Prasad T1 - Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo JF - Acta biomaterialia N2 - 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 engineeredArcGels-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. Statement of Significance In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo implantation in ectopic site of nude mice and (ii) short in vitro culture (3 days) followed by implantation to induce de novo cartilage formation. Softer and fast degrading ArcGel were better at promoting chondrogenesis in vitro, while stiffer and slow degrading ArcGel were strikingly superior in both maintaining chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings highlight the importance of the interplay between scaffold mechanics and degradation in chondrogenesis. KW - Cartilage repair KW - Scaffold stiffness KW - Scaffold contraction KW - Scaffold degradation KW - Matrix metalloproteinase KW - Hypoxia Y1 - 2018 U6 - https://doi.org/10.1016/j.actbio.2018.01.025 SN - 1742-7061 SN - 1878-7568 VL - 69 SP - 83 EP - 94 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Brunacci, Nadia A1 - Neffe, Axel T. A1 - Wischke, Christian A1 - Naolou, Toufik A1 - Nöchel, Ulrich A1 - Lendlein, Andreas T1 - Oligodepsipeptide (nano)carriers BT - computational design and analysis of enhanced drug loading JF - Journal of controlled release N2 - 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 similar to 10 times higher solid state solubility of DXM in OBMD than in PLGA. DXM-loaded particles of similar to 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. KW - Oligodepsipeptide KW - Drug loading KW - Nanoparticles KW - Docking study KW - Molecular interaction design Y1 - 2019 U6 - https://doi.org/10.1016/j.jconrel.2019.03.004 SN - 0168-3659 SN - 1873-4995 VL - 301 SP - 146 EP - 156 PB - Elsevier CY - Amsterdam 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 - Zhang, Nan A1 - Said, Andre A1 - Wischke, Christian A1 - Kral, Vivian A1 - Brodwolf, Robert A1 - Volz, Pierre A1 - Boreham, Alexander A1 - Gerecke, Christian A1 - Li, Wenzhong A1 - Neffe, Axel T. A1 - Kleuser, Burkhard A1 - Alexiev, Ulrike A1 - Lendlein, Andreas A1 - Schäfer-Korting, Monika T1 - Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles - Composition-dependent skin penetration enhancement of a dye probe and biocompatibility JF - European Journal of Pharmaceutics and Biopharmaceutics N2 - 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. Hence, systematic variations of nanoparticle properties allows gaining insights into critical criteria for biocompatibility and functionality of novel nanocarriers for topical drug delivery and risks associated with environmental exposure. KW - Biocompatibility testing KW - Drug delivery systems KW - Nanoparticle KW - Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] KW - Polymers KW - Skin absorption Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2016.10.019 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 66 EP - 75 PB - Elsevier CY - Amsterdam 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 - Folikumah, Makafui Yao A1 - Neffe, Axel T. A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Thiol Michael-Type reactions of optically active mercapto-acids in aqueous medium JF - MRS advances : a journal of the Materials Research Society N2 - 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. KW - biomaterial KW - biomedical KW - biomimetic (chemical reaction) KW - chemical synthesis Y1 - 2019 U6 - https://doi.org/10.1557/adv.2019.308 SN - 2059-8521 VL - 4 IS - 46-47 SP - 2515 EP - 2525 PB - Springer Nature Switzerland AG CY - Cham ER - TY - JOUR A1 - Zhang, Shanshan A1 - Liu, Yue A1 - Machatschek, Rainhard Gabriel A1 - Lendlein, Andreas T1 - Ultrathin collagen type I films formed at the air-water interface JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - Collagen-based biomaterials with oriented fibrils have shown great application potential in medicine. However, it is still challenging to control the type I collagen fibrillogenesis in ultrathin films. Here, we report an approach to produce cohesive and well-organized type I collagen ultrathin films of about 10 nm thickness using the Langmuir-Blodgett technique. Ellipsometry, rheology, and Brewster angle microscopy are applied to investigate in situ how the molecules behave at the air-water interface, both at room temperature and 37 degrees C. The interfacial storage modulus observed at room temperature vanishes upon heating, indicating the existence and disappearance of the network structure in the protein nanosheet. The films were spanning over holes as large as 1 mm diameter when transferred at room temperature, proving the strong cohesive interactions. A highly aligned and fibrillar structure was observed by atomic force microscopy (AFM) and optical microscopy. Y1 - 2022 U6 - https://doi.org/10.1557/s43580-021-00160-8 SN - 2059-8521 VL - 7 IS - 4 SP - 56 EP - 62 PB - Springer Nature Switzerland AG CY - Cham ER - TY - JOUR A1 - Tarazona, Natalia A. A1 - Machatschek, Rainhard Gabriel A1 - Lendlein, Andreas T1 - Unraveling the interplay between abiotic hydrolytic degradation and crystallization of bacterial polyesters comprising short and medium side-chain-length Polyhydroxyalkanoates JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - Polyhydroxyalkanoates (PHAs) have attracted attention as degradable (co)polyesters which can be produced by microorganisms with variations in the side chain. This structural variation influences not only the thermomechanical properties of the material but also its degradation behavior. Here, we used Langmuir monolayers at the air-water (A-W) interface as suitable models for evaluating the abiotic degradation of two PHAs with different side-chain lengths and crystallinity. By controlling the polymer state (semi crystalline, amorphous), the packing density, the pH, and the degradation mechanism, we could draw several significant conclusions. (i) The maximum degree of crystallinity for a PHA film to be efficiently degraded up to pH = 12.3 is 40%. (ii) PHA made of repeating units with shorter side-chain length are more easily hydrolyzed under alkaline conditions. The efficiency of alkaline hydrolysis decreased by about 65% when the polymer was 40% crystalline. (iii) In PHA films with a relatively high initial crystallinity, abiotic degradation initiated a chemicrystallization phenomenon, detected as an increase in the storage modulus (E'). This could translate into an increase in brittleness and reduction in the material degradability. Finally, we demonstrate the stability of the measurement system for long-term experiments, which allows degradation conditions for polymers that could closely simulate real-time degradation. Y1 - 2019 U6 - https://doi.org/10.1021/acs.biomac.9b01458 SN - 1525-7797 SN - 1526-4602 VL - 21 IS - 2 SP - 761 EP - 771 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Zhang, Pengfei A1 - Behl, Marc A1 - Balk, Maria A1 - Peng, Xingzhou A1 - Lendlein, Andreas T1 - Shape-programmable architectured hydrogels sensitive to ultrasound JF - Macromolecular rapid communications N2 - On-demand motion of highly swollen polymer systems can be triggered by changes in pH, ion concentrations, or by heat. Here, shape-programmable, architectured hydrogels are introduced, which respond to ultrasonic-cavitation-based mechanical forces (CMF) by directed macroscopic movements. The concept is the implementation and sequential coupling of multiple functions (swellability in water, sensitivity to ultrasound, shape programmability, and shape-memory) in a semi-interpenetrating polymer network (s-IPN). The semi-IPN-based hydrogels are designed to function through rhodium coordination (Rh-s-IPNH). These coordination bonds act as temporary crosslinks. The porous hydrogels with coordination bonds (degree of swelling from 300 +/- 10 to 680 +/- 60) exhibit tensile strength sigma(max) up to 250 +/- 60 kPa. Shape fixity ratios up to 90% and shape recovery ratios up to 94% are reached. Potential applications are switches or mechanosensors. KW - cavitation-based mechanical force KW - rhodium-phosphine coordination bonds KW - semi-IPN hydrogels KW - shape-memory effect Y1 - 2020 U6 - https://doi.org/10.1002/marc.201900658 SN - 1022-1336 SN - 1521-3927 VL - 41 IS - 7 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Behl, Marc A1 - Balk, Maria A1 - Lützow, Karola A1 - Lendlein, Andreas T1 - Impact of block sequence on the phase morphology of multiblock copolymers obtained by high-throughput robotic synthesis JF - European polymer journal : EPJ N2 - The chemical nature, the number length of integrated building blocks, as well as their sequence structure impact the phase morphology of multiblock copolymers (MBC) consisting of two non-miscible block types. We hypothesized that a strictly alternating sequence should favour phase segregation and in this way the elastic properties. A library of well-defined MBCs composed of two different hydrophobic, semi-crystalline blocks providing domains with well-separated melting temperatures (T(m)s) were synthesized from the same type of precursor building blocks as strictly alternating (MBCsalt) or random (MBCsran) MBCs and compared. Three different series of MBCsalt or MBCsran were synthesized by high-throughput synthesis by coupling oligo(e-caprolactone) (OCL) of different molecular weights (2, 4, and 8 kDa) with oligotetrahydrofuran (OTHF, 2.9 kDa) via Steglich esterification in which the molar ratio of the reaction partners was slightly adjusted. Maximum of weight average molecular weight (M-w) were 65,000 g center dot mol(-1), 165,000 g center dot mol(-1), and 168,000 g center dot mol(-1) for MBCsalt and 80,500 g center dot mol(-1), 100,000 g center dot mol(-1), and 147,600 g center dot mol(-1) for MBCsran. When Mw increased, a decrease of both Tms associated to the melting of the OCL and OTHF domains was observed for all MBCs. T-m (OTHF) of MBCsran was always higher than Tm (OTHF) of MBCsalt, which was attributed to a better phase segregation. In addition, the elongation at break of MBCsalt was almost half as high when compared to MBCsran. In this way this study elucidates role of the block length and sequence structure in MBCs and enables a quantitative discussion of the structure-function relationship when two semi-crystalline block segments are utilized for the design of block copolymers. KW - Multiblock copolymers KW - Sequence structure KW - Phase morphology KW - Polymer KW - library KW - Robotic synthesis KW - High-throughput Y1 - 2021 U6 - https://doi.org/10.1016/j.eurpolymj.2020.110207 SN - 0014-3057 SN - 1873-1945 VL - 143 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Hoffmann, Falk A1 - Machatschek, Rainhard Gabriel A1 - Lendlein, Andreas T1 - Analytical model and Monte Carlo simulations of polymer degradation with improved chain cut statistics JF - Journal of materials research : JMR N2 - The degradation of polymers is described by mathematical models based on bond cleavage statistics including the decreasing probability of chain cuts with decreasing average chain length. We derive equations for the degradation of chains under a random chain cut and a chain end cut mechanism, which are compared to existing models. The results are used to predict the influence of internal molecular parameters. It is shown that both chain cut mechanisms lead to a similar shape of the mass or molecular mass loss curve. A characteristic time is derived, which can be used to extract the maximum length of soluble fragments l of the polymer. We show that the complete description is needed to extract the degradation rate constant k from the molecular mass loss curve and that l can be used to design polymers that lose less mechanical stability before entering the mass loss phase. KW - Modeling KW - Degradable KW - Polymer KW - Molecular weight KW - Simulation Y1 - 2022 U6 - https://doi.org/10.1557/s43578-022-00495-4 SN - 0884-2914 SN - 2044-5326 VL - 37 IS - 5 SP - 1093 EP - 1101 PB - Springer CY - Heidelberg ER - 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 -