TY - JOUR A1 - Wang, Weiwei A1 - Kratz, Karl A1 - Behl, Marc A1 - Yan, Wan A1 - Liu, Yue A1 - Xu, Xun A1 - Baudis, Stefan A1 - Li, Zhengdong A1 - Kurtz, Andreas A1 - Lendlein, Andreas A1 - Ma, Nan T1 - The interaction of adipose-derived human mesenchymal stem cells and polyether ether ketone JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Polyether ether ketone (PEEK) as a high-performance, thermoplastic implant material entered the field of medical applications due to its structural function and commercial availability. In bone tissue engineering, the combination of mesenchymal stem cells (MSCs) with PEEK implants may accelerate the bone formation and promote the osseointegration between the implant and the adjacent bone tissue. In this concept the question how PEEK influences the behaviour and functions of MSCs is of great interest. Here the cellular response of human adipose-derived MSCs to PEEK was evaluated and compared to tissue culture plate (TCP) as the reference material. Viability and morphology of cells were not altered when cultured on the PEEK film. The cells on PEEK presented a high proliferation activity in spite of a relatively lower initial cell adhesion rate. There was no significant difference on cell apoptosis and senescence between the cells on PEEK and TCP. The inflammatory cytokines and VEGF secreted by the cells on these two surfaces were at similar levels. The cells on PEEK showed up-regulated BMP2 and down-regulated BMP4 and BMP6 gene expression, whereas no conspicuous differences were observed in the committed osteoblast markers (BGLAP, COL1A1 and Runx2). With osteoinduction the cells on PEEK and TCP exhibited a similar osteogenic differentiation potential. Our results demonstrate the biofunctionality of PEEK for human MSC cultivation and differentiation. Its clinical benefits in bone tissue engineering may be achieved by combining MSCs with PEEK implants. These data may also provide useful information for further modification of PEEK with chemical or physical methods to regulate the cellular processes of MSCs and to consequently improve the efficacy of MSC-PEEK based therapies. KW - Polyether ether ketone KW - mesenchymal stem cells KW - biocompatibility KW - cell-material interaction KW - osteogenic differentiation Y1 - 2015 U6 - https://doi.org/10.3233/CH-152001 SN - 1386-0291 SN - 1875-8622 VL - 61 IS - 2 SP - 301 EP - 321 PB - IOS Press CY - Amsterdam 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 - Krüger, Anne A1 - Becherer, Tobias A1 - Thünemann, Andreas F. A1 - Jung, Friedrich A1 - Haag, Rainer A1 - Lendlein, Andreas T1 - Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility JF - Journal of materials chemistry : B, Materials for biology and medicine N2 - Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo-and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials. Y1 - 2014 U6 - https://doi.org/10.1039/c4tb00184b SN - 2050-750X SN - 2050-7518 VL - 2 IS - 23 SP - 3626 EP - 3635 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Neffe, Axel T. A1 - von Rüsten-Lange, Maik A1 - Braune, Steffen A1 - Lützow, Karola A1 - Roch, Toralf A1 - Richau, Klaus A1 - Krüger, Anne A1 - Becherer, Tobias A1 - Thünemann, Andreas F. A1 - Jung, Friedrich A1 - Haag, Rainer A1 - Lendlein, Andreas T1 - Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility N2 - Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 285 Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-99444 ER - TY - GEN A1 - Balk, Maria A1 - Grijpma, Dirk W. A1 - Lendlein, Andreas T1 - Design and processing of advanced functional polymers for medicine T2 - Polymers for advanced technologies Y1 - 2017 U6 - https://doi.org/10.1002/pat.3980 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1203 EP - 1205 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Lendlein, Andreas A1 - Balk, Maria A1 - Tarazona, Natalia A. A1 - Gould, Oliver E. C. T1 - Bioperspectives for Shape-Memory Polymers as Shape Programmable, Active Materials JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - Within the natural world, organisms use information stored in their material structure to generate a physical response to a wide variety of environmental changes. The ability to program synthetic materials to intrinsically respond to environmental changes in a similar manner has the potential to revolutionize material science. By designing polymeric devices capable of responsively changing shape or behavior based on information encoded into their structure, we can create functional physical behavior, including a shape memory and an actuation capability. Here we highlight the stimuli-responsiveness and shape-changing ability of biological materials and biopolymer-based materials, plus their potential biomedical application, providing a bioperspective on shape-memory materials. We address strategies to incorporate a shape memory (actuation) function in polymeric materials, conceptualized in terms of its relationship with inputs (environmental stimuli) and outputs (shape change). Challenges and opportunities associated with the integration of several functions in a single material body to achieve multifunctionality are discussed. Finally, we describe how elements that sense, convert, and transmit stimuli have been used to create multisensitive materials. Y1 - 2019 U6 - https://doi.org/10.1021/acs.biomac.9b01074 SN - 1525-7797 SN - 1526-4602 VL - 20 IS - 10 SP - 3627 EP - 3640 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Moradian, Hanieh A1 - Lendlein, Andreas A1 - Gossen, Manfred T1 - Strategies for simultaneous and successive delivery of RNA JF - Journal of molecular medicine N2 - Advanced non-viral gene delivery experiments often require co-delivery of multiple nucleic acids. Therefore, the availability of reliable and robust co-transfection methods and defined selection criteria for their use in, e.g., expression of multimeric proteins or mixed RNA/DNA delivery is of utmost importance. Here, we investigated different co- and successive transfection approaches, with particular focus on in vitro transcribed messenger RNA (IVT-mRNA). Expression levels and patterns of two fluorescent protein reporters were determined, using different IVT-mRNA doses, carriers, and cell types. Quantitative parameters determining the efficiency of co-delivery were analyzed for IVT-mRNAs premixed before nanocarrier formation (integrated co-transfection) and when simultaneously transfecting cells with separately formed nanocarriers (parallel co-transfection), which resulted in a much higher level of expression heterogeneity for the two reporters. Successive delivery of mRNA revealed a lower transfection efficiency in the second transfection round. All these differences proved to be more pronounced for low mRNA doses. Concurrent delivery of siRNA with mRNA also indicated the highest co-transfection efficiency for integrated method. However, the maximum efficacy was shown for successive delivery, due to the kinetically different peak output for the two discretely operating entities. Our findings provide guidance for selection of the co-delivery method best suited to accommodate experimental requirements, highlighting in particular the nucleic acid dose-response dependence on co-delivery on the single-cell level. KW - integrated co-transfection KW - parallel co-transfection KW - successive KW - transfection KW - co-expression KW - in vitro synthesized mRNA KW - transfection methods Y1 - 2020 U6 - https://doi.org/10.1007/s00109-020-01956-1 SN - 0946-2716 SN - 1432-1440 VL - 98 IS - 12 SP - 1767 EP - 1779 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Neffe, Axel T. A1 - Zhang, Quanchao A1 - Hommes-Schattmann, Paul J. A1 - Lendlein, Andreas T1 - Ethylene oxide sterilization of electrospun poly(L-lactide)/poly(D-lactide) core/shell nanofibers JF - MRS advances N2 - The application of polymers in medicine requires sterilization while retaining material structure and properties. This demands detailed analysis, which we show exemplarily for the sterilization of PLLA/PDLA core-shell nanofibers with ethylene oxide (EtO). The electrospun patch was exposed to EtO gas (6 vol% in CO2, 1.7 bar) for 3 h at 45 degrees C and 75% rel. humidity, followed by degassing under pressure/vacuum cycles for 12 h. GC-MS analysis showed that no residual EtO was retained. Fiber diameters (similar to 520 +/- 130 nm) of the patches remained constant as observed by electron microscopy. Young's modulus slightly increased and the elongation at break slightly decreased, determined at 37 degrees C. No changes were detected in H-1-NMR spectra, in molar mass distribution (GPC) or in crystallinity measured for annealed samples with comparable thermal history (Wide Angle X-Ray Scattering). Altogether, EtO emerged as suitable sterilization method for polylactide nanofibers with core-shell morphology. Y1 - 2021 U6 - https://doi.org/10.1557/s43580-021-00058-5 SN - 2059-8521 VL - 6 IS - 33 SP - 786 EP - 789 PB - Springer CY - Cham ER - TY - JOUR A1 - Heilmann, Katja A1 - Groth, Thomas A1 - Behrsing, Olaf A1 - Wagner, Albrecht A1 - Schossig-Tiedemann, Michael A1 - Lendlein, Andreas A1 - Micheel, Burkhard T1 - The influence of the chemical composition of cell culture material on the growth and antibody production of hybridoma cells N2 - The multiplication and antibody production of murine hybridoma cells cultured on five different polymer membranes were tested and compared with conventional tissue culture polystyrene (TCPS). Membranes were prepared from polyacrylonitrile (PAN) and acrylonitrile copolymerized with N-vinylpyrrolidone (NVP20, NVP30), Na-methallylsulfonate (NaMAS) and N-(3-amino-propyl-methacrylamide-hydrochloride) (APMA). Cell number and antibody concentration were quantified as criteria for viability and productivity. Adhesion of hybridoma cells was characterized by vital and scanning electron microscopy. The results suggest that a strong adhesion of cells, observed on APMA and TCPS, increased cell growth but reduced monoclonal antibody production. In contrast membranes with lowered adhesivity such as NVP20 provided favourable conditions for monoclonal antibody production. In addition it was shown that this membrane also possessed a minor fouling as indicated by the low decrease of water flux across the membrane after protein adsorption. It was concluded that NVP20 could be a suitable material for the development of hollow fibre membranes for bioreactors. Y1 - 2005 UR - http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3C-4DPYNGY- 4&_coverDate=02%2F09%2F2005&_alid=268995355&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4943&_sort=d&view=c&_acct=C000053886&_v e ER - TY - JOUR A1 - Feng, Y. A1 - Kelch, S. A1 - Rickert, D. A1 - Fuhrmann, R. A1 - Franke, R. P. A1 - Lendlein, Andreas T1 - Biokompatible abbaubare Formgedächtnispolymersysteme als intelligente Implantatmaterialien Y1 - 2004 ER - TY - JOUR A1 - Kelch, S. A1 - Lendlein, Andreas A1 - Schulte, J. T1 - Kunststoffe mit Formgedächtnis : die erstaunlichen Fähigkeiten intelligenter Materialien Y1 - 2004 SN - 0344-5690 ER - TY - JOUR A1 - Rickert, D A1 - Lendlein, Andreas A1 - Kelch, S A1 - Franke, R. P. A1 - Moses, M. A. T1 - Cell proliferation and cellular activity of primary cell cultures of the oral cavity after cell seeding on the surface of a degradable, thermoplastic block copolymer N2 - Using standard cell biological and biochemical methods we were able to test the ability of a degradable, thermoplastic block copolymer to support the adhesion, proliferation, and the cellular activity of primary cell cultures of the oral cavity in vitro. The delicate balance between a group of endogenous enzymes, Matrix Metalloproteinases (MMPs), and their inhibitors (Tissue Inhibitor of MMPs, TIMPs) have a decisive function in the remodeling of the extracellular matrix during processes like wound healing or the integration of biomaterials in surrounding tissues after implantation. Recently developed, biodegradable thermoplastic elastomers with shape-memory properties may be the key to develop new therapeutical options in head and neck surgery. Primary cell cultures of the oral cavity of Sprague-Dawley rats were seeded on the surface of a thermoplastic block copolymer and on a polystyrene surface as control. Conditioned media of the primary cells were analyzed for MMPs and TIMPs after different periods of cell growth. The MMP and TIMP expression was analysed by zymography and a radiometric enzyme assay. No statistically significant differences in the appearance and the kinetic of MMP-1, MMP-2, MMP-9 and TIMPs were detected between cells grown on the polymer surface compared to the control. An appropriate understanding of the molecular processes that regulate cellular growth and integration of a biomaterial in surrounding tissue is the requirement for an optimal adaptation of biodegradable, polymeric biomaterials to the physiological, anatomical, and surgical conditions in vivo to develop new therapeutic options in otolaryngology and head and neck surgery Y1 - 2005 ER - TY - JOUR A1 - Lendlein, Andreas A1 - Kelch, S. A1 - Schulte, J. A1 - Kratz, K. T1 - Shape-memory polymers Y1 - 2004 ER - TY - JOUR A1 - Groth, Thomas A1 - Lendlein, Andreas T1 - In-vivo-Reparatur von Blutgefäßen durch alternierende Adsorption von Polyelektrolyten Y1 - 2004 UR - http://www3.interscience.wiley.com/cgi-bin/fulltext/107614315/PDFSTART ER - TY - JOUR A1 - Santoso, F. A1 - Schroeter, M. A1 - Wagner, Albrecht A1 - Lendlein, Andreas A1 - Sckomaecker, R. T1 - Simultane Funktionalisierung und Porenöffnung von Polyetherimid-Membranen zur Entwicklung neuer Trägermaterialien für die Apharese Y1 - 2004 ER - TY - JOUR A1 - Groth, Thomas A1 - Lendlein, Andreas T1 - Layer-by-layer deposition of polyelectrolytes : a versatile tool for the in vivo repair of blood vessels and the preparation of biocompatible implant coatings Y1 - 2004 ER - TY - JOUR A1 - Rickert, D. A1 - Lendlein, Andreas A1 - Kelch, S. A1 - Moses, M. A. A1 - Franke, R. P. T1 - Biokompatibilitätstestung von bioabbaubaren Shape Memory Polymeren in vivo Y1 - 2004 ER - TY - JOUR A1 - Binzen, Eva A1 - Lendlein, Andreas A1 - Kelch, S. A1 - Rickert, D. A1 - Franke, R. P. T1 - Biomaterial-microvasculature interaction on polymers after implantation in mice Y1 - 2004 ER - TY - JOUR A1 - Rickert, D. A1 - Lendlein, Andreas A1 - Schmidt, A. M. A1 - Kelch, S. A1 - Roehlke, W. A1 - Fuhrmann, R. A1 - Franke, R. P. T1 - In vitro cytotoxicity testing of AB-polymer networks based on oligo(epsilon-caprolactone) segments after different sterilization techniques Y1 - 2003 ER - TY - JOUR A1 - Rickert, D. A1 - Moses, M. A. A1 - Lendlein, Andreas A1 - Kelch, S. A1 - Franke, R. P. T1 - The importance of angiogenesis in the interaction between polymeric biomaterials and surrounding tissue Y1 - 2003 ER - TY - JOUR A1 - Kelch, S. A1 - Lendlein, Andreas A1 - Müllen, A. A1 - Ridder, U. T1 - Textile Polymer Scaffolds for Tissue Engineering Y1 - 2003 ER - TY - JOUR A1 - Kelch, S. A1 - Lendlein, Andreas A1 - Müllen, A. A1 - Ridder, U. T1 - Textile Polymergerüste für das Tissue Engineering Y1 - 2003 ER - TY - JOUR A1 - Rottke, Falko O. A1 - Schulz, Burkhard A1 - Richau, Klaus A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - An ellipsometric approach towards the description of inhomogeneous polymer-based Langmuir layers JF - Beilstein journal of nanotechnology N2 - The applicability of nulling-based ellipsometric mapping as a complementary method next to Brewster angle microscopy (BAM) and imaging ellipsometry (IE) is presented for the characterization of ultrathin films at the air-water interface. First, the methodology is demonstrated for a vertically nonmoving Langmuir layer of star-shaped, 4-arm poly(omega-pentadecalactone) (PPDL-D4). Using nulling-based ellipsometric mapping, PPDL-D4-based inhomogeneously structured morphologies with a vertical dimension in the lower nm range could be mapped. In addition to the identification of these structures, the differentiation between a monolayer and bare water was possible. Second, the potential and limitations of this method were verified by applying it to more versatile Langmuir layers of telechelic poly[(rac-lactide)-co-glycolide]-diol (PLGA). All ellipsometric maps were converted into thickness maps by introduction of the refractive index that was derived from independent ellipsometric experiments, and the result was additionally evaluated in terms of the root mean square roughness, R-q. Thereby, a three-dimensional view into the layers was enabled and morphological inhomogeneity could be quantified. KW - ellipsometric mapping KW - Langmuir monolayer KW - polyester KW - root mean square roughness KW - spectroscopic ellipsometry Y1 - 2016 U6 - https://doi.org/10.3762/bjnano.7.107 SN - 2190-4286 VL - 7 SP - 1156 EP - 1165 PB - Beilstein-Institut zur Förderung der Chemischen Wissenschaften CY - Frankfurt, Main ER - TY - JOUR A1 - Rossberg, Joana A1 - Rottke, Falko O. A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Enzymatic Degradation of Oligo(epsilon-caprolactone)s End-Capped with Phenylboronic Acid Derivatives at the Air-Water Interface JF - Macromolecular rapid communications N2 - The influence of terminal functionalization of oligo(epsilon-caprolactone)s (OCL) with phenylboronic acid pinacol ester or phenylboronic acid on the enzymatic degradation behavior at the air-water interface is investigated by the Langmuir monolayer degradation technique. While the unsubstituted OCL immediately degrades after injection of the enzyme lipase from Pseudomonas cepacia, enzyme molecules are incorporated into the films based on end-capped OCL before degradation. This incorporation of enzymes does not inhibit or suppress the film degradation, but retards it significantly. A specific binding of lipase to the polymer monolayer allows studying the enzymatic activity of bound proteins and the influence on the degradation process. The functionalization of a macromolecule with phenyl boronic acid groups is an approach to investigate their interactions with diol-containing biomolecules like sugars and to monitor their specified impact on the enzymatic degradation behavior at the air-water interface. Y1 - 2016 U6 - https://doi.org/10.1002/marc.201600471 SN - 1022-1336 SN - 1521-3927 VL - 37 SP - 1966 EP - 1971 PB - Wiley-VCH CY - Weinheim ER - TY - GEN A1 - Naolou, Toufik A1 - Rühl, Eckart A1 - Lendlein, Andreas T1 - Nanocarriers BT - Architecture, transport, and topical application of drugs for therapeutic use T2 - European Journal of Pharmaceutics and Biopharmaceutics Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2017.03.004 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 1 EP - 3 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Lendlein, Andreas T1 - Fabrication of reprogrammable shape-memory polymer actuators for robotics T2 - Science robotics N2 - Shape-memory polymer actuators, whose actuation geometry and switching temperatures are reprogrammable by physical fabrication schemes, were recently suggested for robotics with the option for self-healing and degradability. Y1 - 2018 U6 - https://doi.org/10.1126/scirobotics.aat9090 SN - 2470-9476 VL - 3 IS - 18 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Yuan, Jinkai A1 - Neri, Wilfrid A1 - Zakri, Cecile A1 - Merzeau, Pascal A1 - Kratz, Karl A1 - Lendlein, Andreas A1 - Poulin, Philippe T1 - Shape memory nanocomposite fibers for untethered high-energy microengines JF - Science N2 - Classic rotating engines are powerful and broadly used but are of complex design and difficult to miniaturize. It has long remained challenging to make large-stroke, high-speed, high-energy microengines that are simple and robust. We show that torsionally stiffened shape memory nanocomposite fibers can be transformed upon insertion of twist to store and provide fast and high-energy rotations. The twisted shape memory nanocomposite fibers combine high torque with large angles of rotation, delivering a gravimetric work capacity that is 60 times higher than that of natural skeletal muscles. The temperature that triggers fiber rotation can be tuned. This temperature memory effect provides an additional advantage over conventional engines by allowing for the tunability of the operation temperature and a stepwise release of stored energy. Y1 - 2019 U6 - https://doi.org/10.1126/science.aaw3722 SN - 0036-8075 SN - 1095-9203 VL - 365 IS - 6449 SP - 155 EP - 158 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Braune, Steffen A1 - Latour, Robert A. A1 - Reinthaler, Markus A1 - Landmesser, Ulf A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - In Vitro Thrombogenicity Testing of Biomaterials JF - Advanced healthcare materials N2 - The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed. KW - biomaterials KW - blood tests KW - implants KW - in vitro KW - thrombogenicity Y1 - 2019 U6 - https://doi.org/10.1002/adhm.201900527 SN - 2192-2640 SN - 2192-2659 VL - 8 IS - 21 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Krüger-Genge, A. A1 - Braune, S. A1 - Walter, M. A1 - Krengel, M. A1 - Kratz, K. A1 - Küpper, J. H. A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Influence of different surface treatments of poly(n-butyl acrylate) networks on fibroblasts adhesion, morphology and viability JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - BACKGROUND: Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts. RESULTS: Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p<0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743 +/- 434 cells. mm(-2), was about 6.5 times higher than on cPnBA73 with 115 +/- 73 cells. mm(-2). On cPnBA04 about 20% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBAnetworks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA. CONCLUSION: The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment. KW - Biomaterial KW - poly(n-butyl acrylate) KW - fibroblast KW - oxygen plasma KW - fibrinogen KW - cell adhesion KW - focal adhesion KW - actin cytoskeleton KW - viability Y1 - 2018 U6 - https://doi.org/10.3233/CH-189130 SN - 1386-0291 SN - 1875-8622 VL - 69 IS - 1-2 SP - 305 EP - 316 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Krüger-Genge, Anne A1 - Schulz, Christian A1 - Kratz, Karl A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Comparison of two substrate materials used as negative control in endothelialization studies BT - Glass versus polymeric tissue culture plate JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - The endothelialization of synthetic surfaces applied as cardiovascular implant materials is an important issue to ensure the anti-thrombotic quality of a biomaterial. However, the rapid and constant development of a functionallycon-fluent endothelial cell monolayer is challenging. In order to investigate the compatibility of potential implant materials with endothelial cells several in vitro studies are performed. Here, glass and tissue culture plates (TCP) are often used as reference materials for in vitro pre-testing. However, a direct comparison of both substrates is lacking. Therefore, a comparison of study results is difficult, since results are often related to various reference materials. In this study, the endothelialization of glass and TCP was investigated in terms of adherence, morphology, integrity, viability and function using human umbilical vein endothelial cells (HUVEC). On both substrates an almost functionally confluent HUVEC monolayer was developed after nine days of cell seeding with clearly visible cell rims, decreased stress fiber formation and a pronounced marginal filament band. The viability of HUVEC was comparable for both substrates nine days after cell seeding with only a few dead cells. According to that, the cell membrane integrity as well as the metabolic activity showed no differences between TCP and glass. However, a significant difference was observed for the secretion of IL-6 and IL-8. The concentration of both cytokines, which are associated with migratory activity, was increased in the supernatant of HUVEC seeded on TCP. This result matches well with the slightly increased number of adherent HUVEC on TCP. In conclusion, these findings indicate that both reference materials are almost comparable and can be used equivalently as control materials in in vitro endothelialization studies. KW - Negative control KW - endothelial cells KW - glass KW - TCP KW - reference Y1 - 2018 U6 - https://doi.org/10.3233/CH-189904 SN - 1386-0291 SN - 1875-8622 VL - 69 IS - 3 SP - 437 EP - 445 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Jiang, Yi A1 - Mansfeld, Ulrich A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Programmable microscale stiffness pattern of flat polymeric substrates by temperature-memo technology JF - MRS Communications N2 - Temperature-memory technology was utilized to generate flat substrates with a programmable stiffness pattern from cross-linked poly(ethylene-co-vinyl acetate) substrates with cylindrical microstructures. Programmed substrates were obtained by vertical compression at temperatures in the range from 60 to 100 degrees C and subsequent cooling, whereby a flat substrate was achieved by compression at 72 degrees C, as documented by scanning electron microscopy and atomic force microscopy (AFM). AFM nanoindentation experiments revealed that all programmed substrates exhibited the targeted stiffness pattern. The presented technology for generating polymeric substrates with programmable stiffness pattern should be attractive for applications such as touchpads. optical storage, or cell instructive substrates. Y1 - 2019 U6 - https://doi.org/10.1557/mrc.2019.24 SN - 2159-6859 SN - 2159-6867 VL - 9 IS - 1 SP - 181 EP - 188 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Jiang, Yi A1 - Mansfeld, Ulrich A1 - Fang, Liang A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Temperature-induced evolution of microstructures on poly[ethylene-co-(vinyl acetate)] substrates switches their underwater wettability JF - Materials & design N2 - Material surfaces with tailored aerophobicity are crucial for applications where gas bubble wettability has to be controlled, e.g., gas storage and transport, electrodes, bioreactors or medical devices. Here, we present switchable underwater aerophobicity of hydrophobic polymeric substrates, which respond to heat with multilevel micro-and nanotopographical changes. The cross-linked poly[ethylene-co-(vinyl acetate)] substrates possess arrays of microcylinders with a nanorough top surface. It is hypothesized that the specific micro-/nanotopography of the surface allows trapping of a water film at the micro interspace and in this way generates the aerophobic behavior. The structured substrates were programmed to a temporarily stable, nanoscale flat substrate showing aerophilic behavior. Upon heating, the topographical changes caused a switch in contact angle from aerophilic to aerophobic for approaching air bubbles. In this way, the initial adhesion of air bubbles to the programmed flat substrate could be turned into repellence for the recovered substrate surface. The temperature at which the repellence of air bubbles starts can be adjusted from 58 +/- 3 degrees C to 73 +/- 3 degrees C by varying the deformation temperature applied during the temperature-memory programming procedure. The presented actively switching polymeric substrates are attractive candidates for applications, where an on-demand gas bubble repellence is advantageous. (c) 2018 Helmholtz-Zentrum Geesthacht, Zentrum fur Material- und Kustenforschung. Published by Elsevier Ltd. KW - Aerophobicity KW - Temperature-memory effect KW - Switchable wettability KW - Air bubble repellence KW - Thermo-responsive polymer Y1 - 2018 U6 - https://doi.org/10.1016/j.matdes.2018.12.002 SN - 0264-1275 SN - 1873-4197 VL - 163 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Lendlein, Andreas A1 - Gould, Oliver E. C. T1 - Reprogrammable recovery and actuation behaviour of shape-memory polymers JF - Nature reviews. Materials N2 - Shape memory is the capability of a material to be deformed and fixed into a temporary shape. Recovery of the original shape can then be triggered only by an external stimulus. Shape-memory polymers are highly deformable materials that can be programmed to recover a memorized shape in response to a variety of environmental and spatially localized stimuli as a one-way effect. The shape-memory function can also be generated as a reversible effect enabling actuation behaviour through macroscale deformation and processing, specifically by dictating the macromolecular orientation of actuation units and of the skeleton structure of geometry-determining units in the polymers. Shape-memory polymers can be programmed and reprogrammed into arbitrary shapes. Both recovery and actuation behaviour are reprogrammable. In this Review, we outline the common basis and key differences between the two shape-memory behaviours of polymers in terms of mechanism, fabrication schemes and characterization methods. We discuss which combination of macromolecular architecture and macroscale processing is necessary for coordinated, decentralized and responsive physical behaviour. The extraction of relevant thermomechanical information is described, and design criteria are shown for microscale and macroscale morphologies to gain high levels of recovered or actuation strains as well as on-demand 2D-to-3D shape transformations. Finally, real-world applications and key future challenges are highlighted. Y1 - 2019 U6 - https://doi.org/10.1038/s41578-018-0078-8 SN - 2058-8437 VL - 4 IS - 2 SP - 116 EP - 133 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Reinthaler, Markus A1 - Johansson, Johan Backemo A1 - Braune, Steffen A1 - Al-Hindwan, Haitham Saleh Ali A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Shear-induced platelet adherence and activation in an in-vitro dynamic multiwell-plate system JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials. Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne. cm(-2)) and high (arterial shear stress: 22.2 dyne .cm(-2)) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined. Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend. Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions. Y1 - 2019 U6 - https://doi.org/10.3233/CH-189410 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 2 SP - 183 EP - 191 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Kuhnla, A. A1 - Reinthaler, Markus A1 - Braune, Steffen A1 - Maier, A. A1 - Pindur, Gerhard A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80-98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3% +/- 3.3% to 10.9% +/- 5.9%). The maximum induced aggregation decreased with age for ristocetin (from 85.8% +/- 7.2% to 75.0% +/- 7.8%), ADP (from 88.5% +/- 4.6% to 64.8% +/- 7.3%) and collagen (from 89.5% +/- 3.0% to 64.0% +/- 4.0%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed "platelet exhaustion". In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans. Y1 - 2019 U6 - https://doi.org/10.3233/CH-199006 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 4 SP - 425 EP - 435 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Li, Zhengdong A1 - Xu, Xun A1 - Wang, Weiwei A1 - Kratz, Karl A1 - Sun, Xianlei A1 - Zou, Jie A1 - Deng, Zijun A1 - Jung, Friedrich Wilhelm A1 - Gossen, Manfred A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells. KW - Mesenchymal stem cells KW - precondition KW - microstructure KW - migration KW - FAK-MAPK Y1 - 2017 U6 - https://doi.org/10.3233/CH-179208 SN - 1386-0291 SN - 1875-8622 VL - 67 SP - 267 EP - 278 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Zou, Jie A1 - Wang, Weiwei A1 - Neffe, Axel T. A1 - Xu, Xun A1 - Li, Zhengdong A1 - Deng, Zijun A1 - Sun, Xianlei A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel) JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840 +/- 120 mu m after 4 days, and distributed in the whole scaffold (2mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55 +/- 0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93 +/- 1%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration. KW - Mesenchymal stem cells KW - gelatin based scaffold KW - adipose tissue regeneration KW - adipogenic differentiation Y1 - 2017 U6 - https://doi.org/10.3233/CH-179210 SN - 1386-0291 SN - 1875-8622 VL - 67 IS - 3-4 SP - 297 EP - 307 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Bäckemo, Johan Dag Valentin A1 - Liu, Yue A1 - Lendlein, Andreas T1 - Bio-inspired and computer-supported design of modulated shape changes in polymer materials JF - MRS communications / a publication of the Materials Research Society N2 - The Venus flytrap is a fascinating plant with a finely tuned mechanical bi-stable system, which can switch between mono- and bi-stability. Here, we combine geometrical design of compliant mechanics and the function of shape-memory polymers to enable switching between bi- and mono-stable states. Digital design and modelling using the Chained Beam Constraint Model forecasted two geometries, which were experimentally realized as structured films of cross-linked poly[ethylene-co-(vinyl acetate)] supported by digital manufacturing. Mechanical evaluation confirmed our predicted features. We demonstrated that a shape-memory effect could switch between bi- and mono-stability for the same construct, effectively imitating the Venus flytrap. KW - Additive manufacturing KW - Biomimetic KW - Shape memory KW - Modelling KW - Polymer Y1 - 2021 U6 - https://doi.org/10.1557/s43579-021-00056-6 SN - 2159-6867 VL - 11 IS - 4 SP - 462 EP - 469 PB - Springer CY - Berlin ER - TY - JOUR A1 - Liu, Yue A1 - Gould, Oliver E. C. A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Shape-memory actuation of individual micro-/nanofibers JF - MRS Advances N2 - Advances in the fabrication and characterization of polymeric nanomaterials has greatly advanced the miniaturization of soft actuators, creating materials capable of replicating the functional physical behavior previously limited to the macroscale. Here, we demonstrate how a reversible shape-memory polymer actuation can be generated in a single micro/nano object, where the shape change during actuation of an individual fiber can be dictated by programming using an AFM-based method. Electrospinning was used to prepare poly(epsilon-caprolactone) micro-/nanofibers, which were fixed and crosslinked on a structured silicon wafer. The programming as well as the observation of recovery and reversible displacement of the fiber were performed by vertical three point bending, using an AFM testing platform introduced here. A plateau tip was utilized to improve the stability of the fiber contact and working distance, enabling larger deformations and greater rbSMPA performance. Values for the reversible elongation of epsilon(rev)= 3.4 +/- 0.1% and 10.5 +/- 0.1% were obtained for a single micro (d = 1.0 +/- 0.2 mu m) and nanofiber (d = 300 +/- 100 nm) in cyclic testing between the temperatures 10 and 60 degrees C. The reversible actuation of the nanofiber was successfully characterized for 10 cycles. The demonstration and characterization of individual shape-memory nano and microfiber actuators represents an important step in the creation of miniaturized robotic devices capable of performing complex physical functions at the length scale of cells and structural component of the extracellular matrix. Y1 - 2020 U6 - https://doi.org/10.1557/adv.2020.276 SN - 2059-8521 VL - 5 IS - 46-47 SP - 2391 EP - 2399 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Liu, Yue A1 - Gould, Oliver E. C. A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - On demand sequential release of (sub)micron particles controlled by size and temperature JF - Small : nano micro N2 - Polymeric devices capable of releasing submicron particles (subMP) on demand are highly desirable for controlled release systems, sensors, and smart surfaces. Here, a temperature-memory polymer sheet with a programmable smooth surface served as matrix to embed and release polystyrene subMP controlled by particle size and temperature. subMPs embedding at 80 degrees C can be released sequentially according to their size (diameter D of 200 nm, 500 nm, 1 mu m) when heated. The differences in their embedding extent are determined by the various subMPs sizes and result in their distinct release temperatures. Microparticles of the same size (D approximate to 1 mu m) incorporated in films at different programming temperatures T-p (50, 65, and 80 degrees C) lead to a sequential release based on the temperature-memory effect. The change of apparent height over the film surface is quantified using atomic force microscopy and the realization of sequential release is proven by confocal laser scanning microscopy. The demonstration and quantification of on demand subMP release are of technological impact for assembly, particle sorting, and release technologies in microtechnology, catalysis, and controlled release. KW - on demand particle release KW - temperature-memory effect KW - thermosensitive KW - polymer surface Y1 - 2022 U6 - https://doi.org/10.1002/smll.202104621 SN - 1613-6810 SN - 1613-6829 VL - 18 IS - 5 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Moradian, Hanieh A1 - Gossen, Manfred A1 - Lendlein, Andreas T1 - Co-delivery of genes can be confounded by bicistronic vector design JF - MRS Communications N2 - Maximizing the efficiency of nanocarrier-mediated co-delivery of genes for co-expression in the same cell is critical for many applications. Strategies to maximize co-delivery of nucleic acids (NA) focused largely on carrier systems, with little attention towards payload composition itself. Here, we investigated the effects of different payload designs: co-delivery of two individual "monocistronic" NAs versus a single bicistronic NA comprising two genes separated by a 2A self-cleavage site. Unexpectedly, co-delivery via the monocistronic design resulted in a higher percentage of co-expressing cells, while predictive co-expression via the bicistronic design remained elusive. Our results will aid the application-dependent selection of the optimal methodology for co-delivery of genes. KW - Molecular KW - Packaging KW - Protein Y1 - 2022 U6 - https://doi.org/10.1557/s43579-021-00128-7 SN - 2159-6859 SN - 2159-6867 VL - 12 IS - 2 SP - 145 EP - 153 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Lendlein, Andreas A1 - Heuchel, Matthias T1 - Shape-memory polymers designed in view of thermomechanical energy storage and conversion systems BT - Effective temporary shape fixation by strain-induced formation of supramolecular nanostructures enables high energy density one-way shape-memory polymers JF - ACS central science KW - Actuators KW - Deformation KW - Energy KW - Energy storage KW - Polymers Y1 - 2021 U6 - https://doi.org/10.1021/acscentsci.1c01032 SN - 2374-7951 VL - 7 IS - 10 SP - 1599 EP - 1601 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulation of mesenchymal stem cell migration using programmable polymer sheet actuators JF - MRS advances N2 - Recruitment of mesenchymal stem cells (MSCs) to damaged tissue is a crucial step to modulate tissue regeneration. Here, the migration of human adipose-derived stem cells (hADSCs) responding to thermal and mechanical stimuli was investigated using programmable shape-memory polymer actuator (SMPA) sheets. Changing the temperature repetitively between 10 and 37 degrees C, the SMPA sheets are capable of reversibly changing between two different pre-defined shapes like an artificial muscle. Compared to non-actuating sheets, the cells cultured on the programmed actuating sheets presented a higher migration velocity (0.32 +/- 0.1 vs. 0.57 +/- 0.2 mu m/min). These results could motivate the next scientific steps, for example, to investigate the MSCs pre-loaded in organoids towards their migration potential. Y1 - 2020 U6 - https://doi.org/10.1557/adv.2020.235 SN - 2059-8521 VL - 5 IS - 46-47 SP - 2381 EP - 2390 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Wang, Weiwei A1 - Xu, Xun A1 - Li, Zhengdong A1 - Kratz, Karl A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulating human mesenchymal stem cells using poly(n-butyl acrylate) networks in vitro with elasticity matching human arteries JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Non-swelling hydrophobic poly(n-butyl acrylate) network (cPnBA) is a candidate material for synthetic vascular grafts owing to its low toxicity and tailorable mechanical properties. Mesenchymal stem cells (MSCs) are an attractive cell type for accelerating endothelialization because of their superior anti-thrombosis and immune modulatory function. Further, they can differentiate into smooth muscle cells or endothelial-like cells and secret pro-angiogenic factors such as vascular endothelial growth factor (VEGF). MSCs are sensitive to the substrate mechanical properties, with the alteration of their major cellular behavior and functions as a response to substrate elasticity. Here, we cultured human adipose-derived mesenchymal stem cells (hADSCs) on cPnBAs with different mechanical properties (cPnBA250, Young’s modulus (E) = 250 kPa; cPnBA1100, E = 1100 kPa) matching the elasticity of native arteries, and investigated their cellular response to the materials including cell attachment, proliferation, viability, apoptosis, senescence and secretion. The cPnBA allowed high cell attachment and showed negligible cytotoxicity. F-actin assembly of hADSCs decreased on cPnBA films compared to classical tissue culture plate. The difference of cPnBA elasticity did not show dramatic effects on cell attachment, morphology, cytoskeleton assembly, apoptosis and senescence. Cells on cPnBA250, with lower proliferation rate, had significantly higher VEGF secretion activity. These results demonstrated that tuning polymer elasticity to regulate human stem cells might be a potential strategy for constructing stem cell-based artificial blood vessels. KW - Poly(n-butyl acrylate) KW - mechanical property KW - vascular graft KW - mesenchymal stem cells KW - VEGF Y1 - 2019 U6 - https://doi.org/10.3233/CH-189418 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 2 SP - 277 EP - 289 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Deng, Zijun A1 - Zou, Jie A1 - Wang, Weiwei A1 - Nie, Yan A1 - Tung, Wing-Tai A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Dedifferentiation of mature adipocytes with periodic exposure to cold JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10 degrees C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37 degrees C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1 alpha, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37 degrees C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells. KW - Adipocyte KW - dedifferentiation KW - cold KW - lipid Y1 - 2019 U6 - https://doi.org/10.3233/CH-199005 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 4 SP - 415 EP - 424 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Nie, Yan A1 - Wang, Weiwei A1 - Xu, Xun A1 - Zou, Jie A1 - Bhuvanesh, Thanga A1 - Schulz, Burkhard A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Enhancement of human induced pluripotent stem cells adhesion through multilayer laminin coating JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Bioengineered cell substrates are a highly promising tool to govern the differentiation of stem cells in vitro and to modulate the cellular behavior in vivo. While this technology works fine for adult stem cells, the cultivation of human induced pluripotent stem cells (hiPSCs) is challenging as these cells typically show poor attachment on the bioengineered substrates, which among other effects causes substantial cell death. Thus, very limited types of surfaces have been demonstrated suitable for hiPSC cultures. The multilayer coating approach that renders the surface with diverse chemical compositions, architectures, and functions can be used to improve the adhesion of hiPSCs on the bioengineered substrates. We hypothesized that a multilayer formation based on the attraction of molecules with opposite charges could functionalize the polystyrene (PS) substrates to improve the adhesion of hiPSCs. Polymeric substrates were stepwise coated, first with dopamine to form a polydopamine (PDA) layer, second with polylysine and last with Laminin-521. The multilayer formation resulted in the variation of hydrophilicity and chemical functionality of the surfaces. Hydrophilicity was detected using captive bubble method and the amount of primary and secondary amines on the surface was quantified by fluorescent staining. The PDA layer effectively immobilized the upper layers and thereby improved the attachment of hiPSCs. Cell adhesion was enhanced on the surfaces coated with multilayers, as compared to those without PDA and/or polylysine. Moreover, hiPSCs spread well over this multilayer laminin substrate. These cells maintained their proliferation capacity and differentiation potential. The multilayer coating strategy is a promising attempt for engineering polymer-based substrates for the cultivation of hiPSCs and of interest for expanding the application scope of hiPSCs. KW - Polymeric substrate KW - surface coating KW - induced pluripotent stem cells KW - cell adhesion Y1 - 2019 U6 - https://doi.org/10.3233/CH-189318 SN - 1386-0291 SN - 1875-8622 VL - 70 IS - 4 SP - 531 EP - 542 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Bhuvanesh, Thanga A1 - Saretia, Shivam A1 - Roch, Toralf A1 - Schöne, Anne-Christin A1 - Rottke, Falko O. A1 - Kratz, Karl A1 - Wang, Weiwei A1 - Ma, Nan A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells JF - Polymers for advanced technologies N2 - Glycoproteins adsorbing on an implant upon contact with body fluids can affect the biological response in vitro and in vivo, depending on the type and conformation of the adsorbed biomacromolecules. However, this process is poorly characterized and so far not controllable. Here, protein monolayers of high molecular cohesion with defined density are transferred onto polymeric substrates by the Langmuir-Schaefer (LS) technique and were compared with solution deposition (SO) method. It is hypothesized that on polydimethylsiloxane (PDMS), a substrate with poor cell adhesion capacity, the fibronectin (FN) layers generated by the LS and SO methods will differ in their organization, subsequently facilitating differential stem cell adhesion behavior. Indeed, atomic force microscopy visualization and immunofluorescence images indicated that organization of the FN layer immobilized on PDMS was uniform and homogeneous. In contrast, FN deposited by SO method was rather heterogeneous with appearance of structures resembling protein aggregates. Human mesenchymal stem cells showed reduced absolute numbers of adherent cells, and the vinculin expression seemed to be higher and more homogenously distributed after seeding on PDMS equipped with FN by LS in comparison with PDMS equipped with FN by SO. These divergent responses could be attributed to differences in the availability of adhesion molecule ligands such as the Arg-Gly-Asp (RGD) peptide sequence presented at the interface. The LS method allows to control the protein layer characteristics, including the thickness and the protein orientation or conformation, which can be harnessed to direct stem cell responses to defined outcomes, including migration and differentiation. Copyright (c) 2016 John Wiley & Sons, Ltd. KW - Langmuir-Schaefer method KW - protein adsorption KW - stem cell adhesion KW - cell culture KW - fibronectin Y1 - 2017 U6 - https://doi.org/10.1002/pat.3910 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1305 EP - 1311 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Saretia, Shivam A1 - Machatschek, Rainhard Gabriel A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Reversible 2D networks of oligo(epsilon-caprolactone) at the air-water interface JF - Biomedical Materials N2 - Hydroxyl terminated oligo(epsilon-caprolactone) (OCL) monolayers were reversibly cross-linked forming two dimensional networks (2D) at the air-water interface. The equilibrium reaction with glyoxal as the cross-linker is pH-sensitive. Pronounced contraction in the area of the prepared 2DOCL films in dependence of surface pressure and time revealed the process of the reaction. Cross-linking inhibited crystallization and retarded enzymatic degradation of the OCLfilm. Altering the subphase pH led to a cleavage of the covalent acetal cross-links. The reversibility of the covalent acetal cross-links was proved by observing an identical isotherm as non-cross-linked sample. Besides as model systems, these customizable reversible OCL2D networks are intended for use as pHresponsive drug delivery systems or functionalized cell culture substrates. KW - poly(epsilon-caprolactone) KW - langmuir monolayer KW - two dimensional network KW - crystallization KW - cross-linking Y1 - 2019 U6 - https://doi.org/10.1088/1748-605X/ab0cef SN - 1748-6041 SN - 1748-605X VL - 14 IS - 3 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Machatschek, Rainhard Gabriel A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - The influence of pH on the molecular degradation mechanism of PLGA JF - MRS Advances N2 - Poly[(rac-lactide)-co-glycolide] (PLGA) is used in medicine to provide mechanical support for healing tissue or as matrix for controlled drug release. The properties of this copolymer depend on the evolution of the molecular weight of the material during degradation. which is determined by the kinetics of the cleavage of hydrolysable bonds. The generally accepted description of the degradation of PLGA is a random fragmentation that is autocatalyzed by the accumulation of acidic fragments inside the bulk material. Since mechanistic studies with lactide oligomers have concluded a chain-end scission mechanism and monolayer degradation experiments with polylactide found no accelerated degradation at lower pH, we hypothesize that the impact of acidic fragments on the molecular degradation kinetics of PLGA is overestimated By means of the Langmuir monolayer degradation technique. the molecular degradation kinetics of PLGA at different pH could be determined. Protons did not catalyze the degradation of PLGA. The molecular mechanism at neutral pH and low pH is a combination of random and chainend-cut events, while the degradation under strongly alkaline conditions is determined by rapid chainend cuts. We suggest that the degradation of bulk PLGA is not catalyzed by the acidic degradation products. Instead. increased concentration of small fragments leads to accelerated mass loss via fast chain-end cut events. In the future, we aim to substantiate the proposed molecular degradation mechanism of PLGA with interfacial rheology. Y1 - 2018 U6 - https://doi.org/10.1557/adv.2018.602 SN - 2059-8521 VL - 3 IS - 63 SP - 3883 EP - 3889 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Machatschek, Rainhard Gabriel A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Langmuir Monolayers as Tools to Study Biodegradable Polymer Implant Materials JF - Macromolecular rapid communications N2 - Langmuir monolayers provide a fast and elegant route to analyze the degradation behavior of biodegradable polymer materials. In contrast to bulk materials, diffusive transport of reactants and reaction products in the (partially degraded) material can be neglected at the air-water interface, allowing for the study of molecular degradation kinetics in experiments taking less than a day and in some cases just a few minutes, in contrast to experiments with bulk materials that can take years. Several aspects of the biodegradation behavior of polymer materials, such as the interaction with biomolecules and degradation products, are directly observable. Expanding the technique with surface-sensitive instrumental techniques enables evaluating the evolution of the morphology, chemical composition, and the mechanical properties of the degrading material in situ. The potential of the Langmuir monolayer degradation technique as a predictive tool for implant degradation when combined with computational methods is outlined, and related open questions and strategies to overcome these challenges are pointed out. KW - biomaterial characterization KW - langmuir monolayers KW - polymer degradation KW - predictive characterization tools Y1 - 2018 U6 - https://doi.org/10.1002/marc.201800611 SN - 1022-1336 SN - 1521-3927 VL - 40 IS - 1 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Lützow, Karola A1 - Weigel, Thomas A1 - Lendlein, Andreas T1 - Solvent-based fabrication method for magnetic, shape-memory nanocomposite foams JF - MRS advances N2 - This paper presents shape-memory foams that can be temporarily fixed in their compressed state and be expanded on demand. Highly porous, nanocomposite foams were prepared from a solution of polyetherurethane with suspended nanoparticles (mean aggregate size 90 nm) which have an iron(III) oxide core with a silica shell. The polymer solution with suspended nanoparticles was cooled down to -20 degrees C in a two-stage process, which was followed by freeze-drying. The average pore size increases with decreasing concentration of nanoparticles from 158 mu m to 230 mu m while the foam porosity remained constant. After fixation of a temporary form of the nanocomposite foams, shape recovery can be triggered either by heat or by exposure to an alternating magnetic field. Compressed foams showed a recovery rate of up to 76 +/- 4% in a thermochamber at 80 degrees C, and a slightly lower recovery rate of up to 65 +/- 4% in a magnetic field. KW - composite KW - foam KW - polymer KW - magnetic KW - shape memory Y1 - 2020 U6 - https://doi.org/10.1557/adv.2019.422 SN - 2059-8521 VL - 5 IS - 14-15 SP - 785 EP - 795 PB - Cambridge Univ. Press CY - Cambridge ER -