@article{BhuvaneshSaretiaRochetal.2017, author = {Bhuvanesh, Thanga and Saretia, Shivam and Roch, Toralf and Sch{\"o}ne, Anne-Christin and Rottke, Falko O. and Kratz, Karl and Wang, Weiwei and Ma, Nan and Schulz, Burkhard and Lendlein, Andreas}, title = {Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3910}, pages = {1305 -- 1311}, year = {2017}, abstract = {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.}, language = {en} } @article{BlockiLoewenbergJiangetal.2017, author = {Blocki, Anna and L{\"o}wenberg, Candy and Jiang, Yi and Kratz, Karl and Neffe, Axel T. and Jung, Friedrich and Lendlein, Andreas}, title = {Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3947}, pages = {1245 -- 1251}, year = {2017}, abstract = {Gelatin-based hydrogels offer various biochemical cues that support encapsulated cells and are therefore suitable as cell delivery vehicles in regenerative medicine. However, besides the biochemical signals, biomechanical cues are crucial to ensure an optimal support of encapsulated cells. Hence, we aimed to correlate the cellular response of encapsulated cells to macroscopic and microscopic elastic properties of glycidylmethacrylate (GMA)-functionalized gelatin-based hydrogels. To ensure that different observations in cellular behavior could be attributed to differences in elastic properties, an identical concentration as well as degree of functionalization of biopolymers was utilized to form covalently crosslinked hydrogels. Elastic properties were merely altered by varying the average gelatin-chain length. Hydrogels exhibited an increased degree of swelling and a decreased bulk elastic modulus G with prolonged autoclaving of the starting solution. This was accompanied by an increase of hydrogel mesh size and thus by a reduction of crosslinking density. Tougher hydrogels retained the largest amount of cells; however, they also interfered with cell viability. Softer gels contained a lower cell density, but supported cell elongation and viability. Observed differences could be partially attributed to differences in bulk properties, as high crosslinking densities interfere with diffusion and cell spreading and thus can impede cell viability. Interestingly, a microscopic elastic modulus in the range of native soft tissue supported cell viability and elongation best while ensuring a good cell entrapment. In conclusion, gelatin-based hydrogels providing a soft tissue-like microenvironment represent adequate cell delivery vehicles for tissue engineering approaches. Copyright (c) 2016 John Wiley \& Sons, Ltd.}, language = {en} } @article{FarhanRudolphKratzetal.2018, author = {Farhan, Muhammad and Rudolph, Tobias and Kratz, Karl and Lendlein, Andreas}, title = {Torsional Fiber Actuators from Shape-memory Polymer}, series = {MRS Advances}, volume = {3}, journal = {MRS Advances}, number = {63}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2018.621}, pages = {3861 -- 3868}, year = {2018}, abstract = {Humanoid robots, prosthetic limbs and exoskeletons require soft actuators to perform their primary function, which is controlled movement. In this wont we explored whether crosslinked poly[ethylene-co-(vinyl acetate)] (cPEVA) fibers, with different vinyl acetate (VA) content can serve as torsional fiber actuators. exhibiting temperature controlled reversible rotational changes. Broad melting transitions ranging from 50 to 90 degrees C for cPEVA18-165 or from 40 to 80 degrees C for cPEVA28-165 fibers in combination with complete crystallization at temperatures around 10 degrees C make them suitable actuating materials with adjustable actuation temperature ranges between 10 and 70 degrees C during repetitive cooling and heating. The obtained fibers exhibited a circular cross section with diameters around 0.4 +/- 0.1 mm, while a length of 4 cm was employed for the investigation of reversible rotational actuation after programming by twist insertion using 30 complete rotations at a temperature above melting transition. Repetitive heating and cooling between 10 to 60 degrees C or 70 degrees C of one-end-tethered programmed fibers revealed reversible rotations and torsional force. During cooling 3 +/- 1 complete rotations (Delta theta(r) = + 1080 +/- 360 degrees) in twisting direction were observed, while 4 +/- 1 turns in the opposite direction (Delta theta(r) = - 1440 +/- 1360 degrees) were found during heating. Such torsional fiber actuators, which are capable of approximately one rotation per cm fiber length, can serve as miniaturized rotary motors to provide rotational actuation in futuristic humanoid robots.}, language = {en} } @article{HaaseKrostSauteretal.2017, author = {Haase, Tobias and Krost, Annalena and Sauter, Tilman and Kratz, Karl and Peter, Jan and Kamann, Stefanie and Jung, Friedrich and Lendlein, Andreas and Zohlnh{\"o}fer, Dietlind and R{\"u}der, Constantin}, title = {In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds}, series = {Journal of Tissue Engineering and Regenerative Medicine}, volume = {11}, journal = {Journal of Tissue Engineering and Regenerative Medicine}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {1932-6254}, doi = {10.1002/term.2002}, pages = {1034 -- 1044}, year = {2017}, abstract = {Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7days after implantation and remained stable until 28days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing.}, language = {en} } @article{HeuchelGerberKratzetal.2017, author = {Heuchel, Matthias and Gerber, David and Kratz, Karl and Lendlein, Andreas}, title = {Morphological analysis of differently sized highly porous poly(ether imide) microparticles by mercury porosimetry}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3973}, pages = {1269 -- 1277}, year = {2017}, abstract = {Highly porous poly(ether imide) (PEI) microparticles prepared by a spraying/coagulation process are discussed as candidate adsorber materials for apheresis applications, i.e. removal of uremic toxins from the blood of renal failure patients. PEI particles obtained by the aforementioned procedure can have a broad size distribution with particle diameters ranging from 20 to 800 mu m. In order to further estimate the adsorption behavior of PEI microparticles packed in application relevant apheresis modules, a quantitative information about the relation between particle size and pore morphology is required. In this study, we explored whether the intraparticle porosity of PEI microparticles varies with altering the diameter of the particulate adsorbers. By an analytical wet sieving procedure, the obtained PEI microparticles were separated into five size fractions, which were analyzed by mercury intrusion porosimetry, nitrogen adsorption, and scanning electron microscopy. Mercury intrusion porosimetry revealed for all size fractions high porosity values in the range from 78\% to 84\% with pore diameters in the range from 10 to 1000nm. A bimodal pore size distribution was found having a first peak at around 100nm, while a second pronounced peak maximum was found at higher pore sizes that increased with raising particle diameter from 300nm for the smallest particle size fraction (50-100 mu m) to 700nm for particles with a diameter of 200 to 250 mu m. Based on these findings, it can be assumed that the main PEI particle size fraction (200-250 mu m) should exhibit the highest adsorption capacity in an apheresis module. Copyright (c) 2016 John Wiley \& Sons, Ltd.}, language = {en} } @article{KruegerGengeDietzeYanetal.2018, author = {Kr{\"u}ger-Genge, Anne and Dietze, Stefanie and Yan, Wan and Liu, Yue and Fang, Liang and Kratz, Karl and Lendlein, Andreas and Jung, Friedrich}, title = {Endothelial cell migration, adhesion and proliferation on different polymeric substrates}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {70}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189317}, pages = {511 -- 529}, year = {2018}, abstract = {BACKGROUND: The formation of a functionally-confluent endothelial cell (EC) monolayer affords proliferation of EC, which only happens in case of appropriate migratory activity. AIM OF THE STUDY: The migratory pathway of human umbilical endothelial cells (HUVEC) was investigated on different polymeric substrates. MATERIAL AND METHODS: Surface characterization of the polymers was performed by contact angle measurements and atomic force microscopy under wet conditions. 30,000 HUVEC per well were seeded on polytetrafluoroethylene (PTFE) (theta(adv) = 119 degrees +/- 2 degrees), on low-attachment plate LAP (theta(adv) = 28 degrees +/- 2 degrees) and on polystyrene based tissue culture plates (TCP, theta(adv) = 22 degrees +/- 1 degrees). HUVEC tracks (trajectories) were recorded by time lapse microscopy and the euclidean distance (straight line between starting and end point), the total distance and the velocities of HUVEC not leaving the vision field were determined. RESULTS: On PTFE, 42 HUVEC were in the vision field directly after seeding. The mean length of single migration steps (SML) was 6.1 +/- 5.2 mu m, the mean velocity (MV) 0.40 +/- 0.3 mu m.min(-1) and the complete length of the trajectory (LT) was 710 +/- 440 mu m. On TCP 82 HUVEC were in the vision field subsequent to seeding. The LT was 840 +/- 550 mu m, the SML 6.1 +/- 5.2 mu m and the MV 0.44 +/- 0.3 mu m.min(-1). The trajectories on LAP differed significantly in respect to SML (2.4 +/- 3.9 mu m, p <0.05), the MV (0.16 +/- 0.3 mu m.min(-1), p <0.05) and the LT (410 +/- 300 mu m, p <0.05), compared to PTFE and TCP. Solely on TCP a nearly confluent EC monolayer developed after three days. While on TCP diffuse signals of vinculin were found over the whole basal cell surface organizing the binding of the cells by focal adhesions, on PTFE vinculin was merely arranged at the cell rims, and on the hydrophilic material (LAP) no focal adhesions were found. CONCLUSION: The study revealed that the wettability of polymers affected not only the initial adherence but also the migration of EC, which is of importance for the proliferation and ultimately the endothelialization of polymer-based biomaterials.}, language = {en} } @article{LiXuWangetal.2017, author = {Li, Zhengdong and Xu, Xun and Wang, Weiwei and Kratz, Karl and Sun, Xianlei and Zou, Jie and Deng, Zijun and Jung, Friedrich Wilhelm and Gossen, Manfred and Ma, Nan and Lendlein, Andreas}, title = {Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {67}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-179208}, pages = {267 -- 278}, year = {2017}, abstract = {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.}, language = {en} } @article{LiuGouldRudolphetal.2020, author = {Liu, Yue and Gould, Oliver E. C. and Rudolph, Tobias and Fang, Liang and Kratz, Karl and Lendlein, Andreas}, title = {Polymeric microcuboids programmable for temperature-memory}, series = {Macromolecular materials and engineering}, volume = {305}, journal = {Macromolecular materials and engineering}, number = {10}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1438-7492}, doi = {10.1002/mame.202000333}, pages = {7}, year = {2020}, abstract = {Microobjects with programmable mechanical functionality are highly desirable for the creation of flexible electronics, sensors, and microfluidic systems, where fabrication/programming and quantification methods are required to fully control and implement dynamic physical behavior. Here, programmable microcuboids with defined geometries are prepared by a template-based method from crosslinked poly[ethylene-co-(vinyl acetate)] elastomers. These microobjects could be programmed to exhibit a temperature-memory effect or a shape-memory polymer actuation capability. Switching temperaturesT(sw)during shape recovery of 55 +/- 2, 68 +/- 2, 80 +/- 2, and 86 +/- 2 degrees C are achieved by tuning programming temperatures to 55, 70, 85, and 100 degrees C, respectively. Actuation is achieved with a reversible strain of 2.9 +/- 0.2\% to 6.7 +/- 0.1\%, whereby greater compression ratios and higher separation temperatures induce a more pronounced actuation. Micro-geometry change is quantified using optical microscopy and atomic force microscopy. The realization and quantification of microparticles, capable of a tunable temperature responsive shape-change or reversible actuation, represent a key development in the creation of soft microscale devices for drug delivery or microrobotics.}, language = {en} } @article{RuederSauterKratzetal.2013, author = {R{\"u}der, Constantin and Sauter, Tilman and Kratz, Karl and Haase, Tobias and Peter, Jan and Jung, Friedrich and Lendlein, Andreas and Zohlnh{\"o}fer, Dietlind}, title = {Influence of fibre diameter and orientation of electrospun copolyetheresterurethanes on smooth muscle and endothelial cell behaviour}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {55}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-131787}, pages = {513 -- 522}, year = {2013}, abstract = {Polymers exhibiting cell-selective effects represent an extensive research field with high relevance for biomedical applications e.g. in the cardiovascular field supporting re-endothelialization while suppressing smooth muscle cell overgrowth. Such an endothelial cell-selective effect could be recently demonstrated for a copolyetheresterurethane (PDC) containing biodegradable poly(p-dioxanone) and poly(epsilon-caprolactone) segments, which selectively enhanced the adhesion of human umbilical vein endothelial cells (HUVEC) while suppressing the attachment of smooth muscle cells (SMC). In this study we investigated the influence of the fibre orientation (random and aligned) and fibre diameter (2 mu m and 500 nm) of electrospun PDC scaffolds on the adhesion, proliferation and apoptosis of HUVEC and SMC. Adhesion, viability and proliferation of HUVEC was diminished when the fibre diameter was reduced to a submicron scale, while the orientation of the microfibres did only slightly influence the cellular behaviour. In contrast, a submicron fibre diameter improved SMC viability. In conclusion, PDC scaffolds with micron-sized single fibres could be promising candidate materials for cell-selective stent coatings.}, language = {en} } @article{SauterGeigerKratzetal.2015, author = {Sauter, Tilman and Geiger, Brett and Kratz, Karl and Lendlein, Andreas}, title = {Encasement of metallic cardiovascular stents with endothelial cell-selective copolyetheresterurethane microfibers}, series = {Polymers for advanced technologies}, volume = {26}, journal = {Polymers for advanced technologies}, number = {10}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3583}, pages = {1209 -- 1216}, year = {2015}, abstract = {Cardiovascular metallic stents established in clinical application are typically coated by a thin polymeric layer on the stent struts to improve hemocompatibility, whereby often a drug is added to the coating to inhibit neointimal hyperplasia. Besides such thin film coatings recently nano/microfiber coated stents are investigated, whereby the fibrous coating was applied circumferential on stents. Here, we explored whether a thin fibrous encasement of metallic stents with preferentially longitudinal aligned fibers and different local fiber densities can be achieved by electrospinning. An elastic degradable copolyetheresterurethane, which is reported to selectively enhance the adhesion of endothelial cells, while simultaneously rejecting smooth muscle cells, was utilized for stent coating. The fibrous stent encasements were microscopically assessed regarding their single fiber diameters, fiber covered area and fiber alignment at three characteristic stent regions before and after stent expansion. Stent coatings with thicknesses in the range from 30 to 50 mu m were achieved via electrospinning with 1,1,1,3,3,3-hexafluoro-2-propanol (HFP)-based polymer solution, while a mixture of HFP and formic acid as solvent resulted in encasements with a thickness below 5 mu m comprising submicron sized single fibers. All polymeric encasements were mechanically stable during expansion, whereby the fibers deposited on the struts remained their position. The observed changes in fiber density and diameter indicated diverse local deformation mechanisms of the microfibers at the different regions between the struts. Based on these results it can be anticipated that the presented fibrous encasement of stents might be a promising alternative to stents with polymeric strut coatings releasing anti-proliferative drugs. Copyright (c) 2015 John Wiley \& Sons, Ltd.}, language = {en} }