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  - 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  - 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  - Neffe, Axel T.
A1  - Izraylit, Victor
A1  - Hommes-Schattmann, Paul J.
A1  - Lendlein, Andreas
T1  - Soft, formstable (Co)polyester blend elastomers
JF  - Nanomaterials : open access journal
N2  - High crystallization rate and thermomechanical stability make polylactide stereocomplexes effective nanosized physical netpoints. Here, we address the need for soft, form-stable degradable elastomers for medical applications by designing such blends from (co)polyesters, whose mechanical properties are ruled by their nanodimensional architecture and which are applied as single components in implants. By careful controlling of the copolymer composition and sequence structure of poly[(L-lactide)-co-(epsilon-caprolactone)], it is possible to prepare hyperelastic polymer blends formed through stereocomplexation by adding poly(D-lactide) (PDLA). Low glass transition temperature T-g <= 0 degrees C of the mixed amorphous phase contributes to the low Young's modulus E. The formation of stereocomplexes is shown in DSC by melting transitions T-m > 190 degrees C and in WAXS by distinct scattering maxima at 2 theta = 12 degrees and 21 degrees. Tensile testing demonstrated that the blends are soft (E = 12-80 MPa) and show an excellent hyperelastic recovery R-rec = 66-85% while having high elongation at break epsilon(b) up to >1000%. These properties of the blends are attained only when the copolymer has 56-62 wt% lactide content, a weight average molar mass >140 kg center dot mol(-1), and number average lactide sequence length >= 4.8, while the blend is formed with a content of 5-10 wt% of PDLA. The devised strategy to identify a suitable copolymer for stereocomplexation and blend formation is transferable to further polymer systems and will support the development of thermoplastic elastomers suitable for medical applications.
KW  - thermoplastic elastomer
KW  - biomaterial
KW  - stereocomplexes
KW  - mechanical
KW  - properties
KW  - form stability
KW  - crystallinity
Y1  - 2021
U6  - https://doi.org/10.3390/nano11061472
SN  - 2079-4991
VL  - 11
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Bhuvanesh, Thanga
A1  - Machatschek, Rainhard Gabriel
A1  - Lysyakova, Liudmila
A1  - Kratz, Karl
A1  - Schulz, Burkhard
A1  - Ma, Nan
A1  - Lendlein, Andreas
T1  - Collagen type-IV Langmuir and Langmuir-Schafer layers as model biointerfaces to direct stem cell adhesion
JF  - Biomedical materials :  materials for tissue engineering and regenerative medicine
N2  - In biomaterial development, the design of material surfaces that mimic the extra-cellular matrix (ECM) in order to achieve favorable cellular instruction is rather challenging. Collagen-type IV (Col-IV), the major scaffolding component of Basement Membranes (BM), a specialized ECM with multiple biological functions, has the propensity to form networks by self-assembly and supports adhesion of cells such as endothelial cells or stem cells. The preparation of biomimetic Col-IV network-like layers to direct cell responses is difficult. We hypothesize that the morphology of the layer, and especially the density of the available adhesion sites, regulates the cellular adhesion to the layer. The Langmuir monolayer technique allows for preparation of thin layers with precisely controlled packing density at the air-water (A-W) interface. Transferring these layers onto cell culture substrates using the Langmuir-Schafer (LS) technique should therefore provide a pathway for preparation of BM mimicking layers with controlled cell adherence properties. In situ characterization using ellipsometry and polarization modulation-infrared reflection absorption spectroscopy of Col-IV layer during compression at the A-W interface reveal that there is linear increase of surface molecule concentration with negligible orientational changes up to a surface pressure of 25 mN m(-1). Smooth and homogeneous Col-IV network-like layers are successfully transferred by LS method at 15 mN m(-1) onto poly(ethylene terephthalate) (PET), which is a common substrate for cell culture. In contrast, the organization of Col-IV on PET prepared by the traditionally employed solution deposition method results in rather inhomogeneous layers with the appearance of aggregates and multilayers. Progressive increase in the number of early adherent mesenchymal stem cells (MSCs) after 24 h by controlling the areal Col-IV density by LS transfer at 10, 15 and 20 mN m(-1) on PET is shown. The LS method offers the possibility to control protein characteristics on biomaterial surfaces such as molecular density and thereby, modulate cell responses.
KW  - collagen-IV
KW  - basement membrane
KW  - Langmuir-Schafer films
KW  - stem cell adhesion
KW  - protein
KW  - ellipsometry
Y1  - 2019
U6  - https://doi.org/10.1088/1748-605X/aaf464
SN  - 1748-6041
SN  - 1748-605X
VL  - 14
IS  - 2
PB  - Inst. of Physics Publ.
CY  - Bristol
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  - Neffe, Axel T.
A1  - Löwenberg, Candy
A1  - Julich-Gruner, Konstanze K.
A1  - Behl, Marc
A1  - Lendlein, Andreas
T1  - Thermally-induced shape-memory behavior of degradable gelatin-based networks
JF  - International journal of molecular sciences
N2  - Shape-memory hydrogels (SMH) are multifunctional, actively-moving polymers of interest in biomedicine. In loosely crosslinked polymer networks, gelatin chains may form triple helices, which can act as temporary net points in SMH, depending on the presence of salts. Here, we show programming and initiation of the shape-memory effect of such networks based on a thermomechanical process compatible with the physiological environment. The SMH were synthesized by reaction of glycidylmethacrylated gelatin with oligo(ethylene glycol) (OEG) alpha,omega-dithiols of varying crosslinker length and amount. Triple helicalization of gelatin chains is shown directly by wide-angle X-ray scattering and indirectly via the mechanical behavior at different temperatures. The ability to form triple helices increased with the molar mass of the crosslinker. Hydrogels had storage moduli of 0.27-23 kPa and Young's moduli of 215-360 kPa at 4 degrees C. The hydrogels were hydrolytically degradable, with full degradation to water-soluble products within one week at 37 degrees C and pH = 7.4. A thermally-induced shape-memory effect is demonstrated in bending as well as in compression tests, in which shape recovery with excellent shape-recovery rates R-r close to 100% were observed. In the future, the material presented here could be applied, e.g., as self-anchoring devices mechanically resembling the extracellular matrix.
KW  - shape-memory hydrogel
KW  - active polymer
KW  - biopolymer
KW  - mechanical
KW  - properties
KW  - degradation
Y1  - 2021
U6  - https://doi.org/10.3390/ijms22115892
SN  - 1422-0067
SN  - 1661-6596
VL  - 22
IS  - 11
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Deng, Zijun
A1  - Wang, Weiwei
A1  - Xua, Xun
A1  - Gould, Oliver E. C.
A1  - Kratz, Karl
A1  - Ma, Nan
A1  - Lendlein, Andreas
T1  - Polymeric sheet actuators with programmable bioinstructivity
JF  - PNAS
N2  - Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.
KW  - reversible shape-memory actuator
KW  - mesenchymal stem cells
KW  - calcium influx
KW  - HDAC1
KW  - RUNX2
Y1  - 2020
U6  - https://doi.org/10.1073/pnas.1910668117
SN  - 1091-6490
VL  - 117
IS  - 4
SP  - 1895
EP  - 1901
PB  - National Academy of Sciences
CY  - Washington, DC
ER  - 
TY  - JOUR
A1  - Lau, Skadi
A1  - Maier, Anna
A1  - Braune, Steffen
A1  - Gossen, Manfred
A1  - Lendlein, Andreas
T1  - Effect of endothelial culture medium composition on platelet responses to polymeric biomaterials
JF  - International journal of molecular sciences
N2  - Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT.
KW  - cyclic olefin copolymer
KW  - poly(tetrafluoroethylene)
KW  - endothelial cells
KW  - platelets
KW  - in vitro thrombogenicity testing
Y1  - 2021
U6  - https://doi.org/10.3390/ijms22137006
SN  - 1422-0067
SN  - 1661-6596
VL  - 22
IS  - 13
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - GEN
A1  - Deng, Zijun
A1  - Wang, Weiwei
A1  - Xua, Xun
A1  - Gould, Oliver E. C.
A1  - Kratz, Karl
A1  - Ma, Nan
A1  - Lendlein, Andreas
T1  - Polymeric sheet actuators with programmable bioinstructivity
T2  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1441 
KW  - reversible shape-memory actuator
KW  - mesenchymal stem cells
KW  - calcium influx
KW  - HDAC1
KW  - RUNX2
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515490
SN  - 1866-8372
IS  - 4
ER  -