# Electrospun Nanofibrous Membranes for Tissue Engineering and Cell Growth
## 4 Gelatin and Collagen  
Collagen belongs to the native extracellular matrix (ECM) of the human body. The ECM is responsible for providing the mechanical structure of tissues, as well as for wound healing and controlling other cellular processes [52]. Thus, collagen belongs to the highly interesting materials for tissue engineering. Gelatin, which is derived from collagen by partial hydrolysis, has partly similar and partly different physical properties, varying depending on the origin and processing of the material [53; 54]. As usual for many biopolymers, collagen and gelatin are water-soluble and thus need a crosslinking step [40]. Alternatively, the water-resistance and mechanical properties can be enhanced by blending them with water-stable polymers. This is why many studies found in the literature report on blends of collagen or gelatin with other polymers. For example, [PERSON] et al. prepared polyurethane/collagen core-shell nanofibers by coaxial electrospinning that were crosslinked by glutaraldehyde (GA) vapor [55]. Thermoplastic polyurethane (TPUs) are known to have not only good mechanical properties, but also good biocompatibility, resulting in their frequent use in implants, catheters, etc. [56]. Special medical-grade TPU can additionally avoid in vivo degradation [57]. The coaxial electrospinning technique used here allows spinning two different polymers through the inner and the outer part of the needle, driven by two independent syringe pumps and fed from separate reservoirs [55]. In comparison with pure collagen, the core-shell fibers showed significantly improved mechanical properties, combined with the highest viability of pig iliac endothelial cells (PIECs) cultured on the different electrospun nanofiber mats, even higher than on pure collagen fibers. All nanofiber mats showed a better cell viability than reference tests on coverslips. The authors mentioned that the fiber diameters, mat porosity, and mechanical properties of the nanofiber mats significantly influenced cell growth and migration, which resulted in compound nanofibers--especially produced by coaxial electrospinning of collagen around TPU--having the best growth conditions. They also mentioned that the coaxially collagen-coated TPU fibers were much more attached cells, while simply coating a pure TPU nanofiber mat macroscopically with collagen did not have the same effect of 3D ingrowth into the scaffold, showing the importance of combining material and structure. Similar results were found by the same group with TPU/collagen blended nanofibers [58]. A polymer blend from collagen and poly((D,L-lactic)-\(co\)-glycolide) (PLGA) was investigated by [PERSON] et al. [59]. PLGA belongs to the synthetic biodegradable polymers, which are often studied for tissue engineering applications, but usually show insufficient cell adhesion and proliferation if used purely [60]. Blending PLGA with collagen, however, led to electrospun nanofiber mats which did not need to be crosslinked to avoid swelling in culture medium and on which human dermal fibroblasts and mice fibroblasts containing green fluorescent protein (GFP) showed a significantly higher viability than on pure PLGA nanofiber mats [59]. This was attributed to the chemical composition of the matrix material, since the fiber diameters were kept constant in all nanofiber mats. The authors explained that collagen and its integrin-binding domains facilitated the cell attachment for anchorage-dependent cell types as the fibroblasts used in this study. A comparison with tissue culture plates additionally showed much higher cell numbers inside the nanofibrous mats due to the available void volume. Quite a different approach was chosen by [PERSON] et al., who combined collagen with chondroite sulfate, a negatively sulfated glycosaminoglycan [61]. The electrospun collagen/chondroitin nanofiber mat was cross-linked with EDC/NHS (1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodimide hydrochloride/\(N\)-hydroxy succinimide), before cytocompatibility was investigated using corneal epithelial cells.