Important in developing new biomaterials is the prevention of unspecific protein adsorption and cell interactions that in vivo can lead to a foreign body reaction. On the other hand, the material should support the growth of a specific cell type in a defined way. We investigate the possibility of manipulating cellular behavior on an intrinsically nonadhesive material by topographic patterning without additional surface chemistry modifications. The biomaterial applied is a hydrogel cross-linked from star-shaped poly(ethylene glycol) macromonomers (starPEG). Cell biological studies with a mouse fibroblast cell line (L929) showed that, while substrates with a smooth surface are nonadhesive, as expected, imprinted topography enabled cell adhesion and spreading. The fibroblasts aligned to micrometer groove patterns and were, depending on the respective dimensions, able to span or enter the grooves. Especially substrates with topography dimensions in the cell size range or smaller (<10 microm) lead to an establishment of stable cell-surface contacts (vinculin and actin accumulation). On micrometer post patterns the cells spread on top of the pillars and wrapped around the structures. The strong influence of the topography shows that nonadhesive materials do not necessarily have to be specifically biofunctionalized to enable cell adhesion. Possible explanations for the peculiar cell behavior are discussed in terms of (initial) protein adsorption and geometry-dependent cytoskeletal arrangements.
In-stent restenosis is still an important issue and stent thrombosis is an unresolved risk after coronary intervention. Biodegradable stents would provide initial scaffolding of the stenosed segment and disappear subsequently. The additive manufacturing technology Selective Laser Melting (SLM) enables rapid, parallel, and raw material saving generation of complex 3- dimensional structures with extensive geometric freedom and is currently in use in orthopedic or dental applications. Here, SLM process parameters were adapted for poly-L-lactid acid (PLLA) and PLLA-co-poly-ε-caprolactone (PCL) powders to generate degradable coronary stent prototypes. Biocompatibility of both polymers was evidenced by assessment of cell morphology and of metabolic and adhesive activity at direct and indirect contact with human coronary artery smooth muscle cells, umbilical vein endothelial cells, and endothelial progenitor cells. γ-sterilization was demonstrated to guarantee safety of SLM-processed parts. From PLLA and PCL, stent prototypes were successfully generated and post-processing by spray- and dip-coating proved to thoroughly smoothen stent surfaces. In conclusion, for the first time, biodegradable polymers and the SLM technique were combined for the manufacturing of customized biodegradable coronary artery stent prototypes. SLM is advocated for the development of biodegradable coronary PLLA and PCL stents, potentially optimized for future bifurcation applications.
Two UV-curable polymers, i.e., a star-shaped poly(ethylene glycol) (PEG) and a linear perfluorinated polyether (PFPE), are investigated as novel biomaterials in a systematic study of the cellular responses to surface chemistry, topography, and elasticity. Based on the wettability it was expected that the two novel biomaterials were too hydrophilic or -phobic, respectively, to support cell adhesion. Indeed, no cell adhesion was observed on the smooth, unstructured elastomers, whereas the materials showed no cytotoxicity. However, when the materials bear defined, topographic patterns (prepared by UV-based imprinting), cells do react strongly to the surfaces; they adhere, spread, and change their shape depending on the geometry of the features. Typically, cells were found to align along line patterns and "float" on pillar structures. It should be noted that the chemistry of the surface is not altered by the imprinting process, hence, there are no biofunctional molecules present at the surface to aid the cell adhesion. Finally, a remarkable effect of elasticity on the cellular behavior was discovered. Thus, the three parameters of chemistry, topography, and elasticity were investigated in- and interdependently, and it was found that the biomaterials may lose their resistance to protein adsorption and cell adhesion depending on the surface topography.
Biomaterials that prevent nonspecific protein adsorption and cell adhesion are of high relevance for diverse applications in tissue engineering and diagnostics. One of the most widely applied materials for this purpose is Poly(ethylene glycol) (PEG). We have investigated how micrometer line topography and substrate elasticity act upon the antiadhesive properties of PEG-based hydrogels. In our studies we apply bulk hydrogel cross-linked from star-shaped poly(ethylene oxide-stat-propylene oxide) macromonomers. Substrate surfaces were topographically patterned via replica molding. Additionally, the mechanical properties were altered by variations in the cross-linking density. Surface patterns with dimensions in the range of the cells' own size, namely 10 μm wide grooves, induced significant cell adhesion and spreading on the Acr-sP(EO-stat-PO) hydrogels. In contrast, there was only little adhesion to smaller and larger pattern sizes and no adhesion at all on the smooth substrates, regardless the rigidity of the gel. The effect of varied substrate stiffness on cell behavior was only manifest in combination with topography. Softer substrates with line patterns lead to significantly higher cell adhesion and spreading than stiff substrates. We conclude that the physical and mechanical surface characteristics can eliminate the nonadhesive properties of PEG-based hydrogels to a large extent. This has to be taken into account when designing surfaces for biomedical application such as scaffolds for tissue engineering which rely on the inertness of PEG.
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