# Tissue Engineering Strategies for Retina Regeneration
## 4 Biomaterials and Scaffolds Used for Tissue Engineering  
### Natural Biomaterials Used as Scaffolds  
Biomaterials mainly include ECM proteins and polysaccharides which possess bioactive properties. The natural polymers used for retinal tissue engineering are easily available and include collagen types I, III, and IV, gelatin, alginates, laminin, fibronectin, matrigel, silk fibroin, and vitronectin. These scaffolds constitute nanofibers that have very similar physiological properties as BM in terms of morphology, mechanical properties, protein concentrations, and biocompatibility. Collagen I is a major component of the inner collagen layer of BM and studies have proved them as a viable substrate for RPE cell reattachment [77]. Usually, this polymer is too thick for subretinal implantation, hence specially designed ultrathin (7 \(\upmu\)m) membranes were designed for testing. [PERSON] et al. [78] showed that ultrathin collagen membranes can remain stable for at least 10 weeks and completely degrade within 24 weeks. By then the transplanted RPE were able to restructure the BM. In another study, collagen films supported by Teflon showed RPE attachment and viability [79]. Human primary RPE cells and the immortalized retinal pigment epithelial cell line (ARPE-19) have been previously cultured on equine, bovine, and rat collagen type I membranes as well as on human collagen type I thin films [80,81]. Gelatin, a denatured form of collagen proteins, is advantageous over collagen because of lower immunogenicity, crosslinking ability, and better solubility in aqueous systems. Gelatin membranes in the shape of a sandwich with encapsulated retinal grafts were used for transplantation studies in rabbits to demonstrate biocompatibility, improved survival, and formation of laminar structures [82]. Gelatin membrane cross-linked with carbodiimide when used for retinal sheet implantation was found to be more stable against hydrolysis and mechanical stress [83].  
Alginate is an anionic polysaccharide that is usually found in the cell walls of brown algae. In a study, a thin film of purified alginate was used to demonstrate its ability to support the growth of RPE cells and their high proliferative rates [84]. In another study, alginate beads were used to demonstrate RPE cell sustenance and proliferation [85]. An arginine-glycine-aspartic-alginate (RGD-alginate) scaffold demonstrated feasibility for cell derivation and transplantation of RPE and neural retina [86]. Bombyx mori silk fibroin (BMSF) that possesses unique structural properties and mechanical strength, is another suitable candidate to be used in the eye [87]. BMSF pre-coated with vitronectin is used to fabricate a membrane up to 3 \(\upmu\)m in thickness as a carrier substrate for human RPE transplantation. Although the cells were grown on BMSF for approximately 8 weeks with expressing RPE characteristics, the duration required to establish the culture was comparatively long [88].  
Recent advances in decellularized scaffold techniques are expected to better preserve tissue architecture and chemistry. [PERSON] et al. [89] used ionic detergents to decellularize bovine eyes and processed them into stable thin films. The decellularized matrix-supported adherence and proliferation of human RPCs. The gene expression of CRX, ROM1, RHODOPSIN, and NRL on these retinal films indicated photoreceptor differentiation tion [90]. In another study, an amniotic membrane was used as a BM substitute, in which it supported RPE ingrowth in the pig eyes with choroidal neovascularization [90]. Areas of hypo and hyperpigmentation observed in this study were attributed to the migration of RPE cells into the affected region in the presence of an amniotic membrane. Interestingly, the amniotic membrane was not stated as being beneficial or detrimental to choroidal neovascularization, as there was an initial hemorrhage but no additional leakage [90].