# Tissue Engineering Strategies for Retina Regeneration
## 4 Biomaterials and Scaffolds Used for Tissue Engineering
### Synthetic Biomaterials Used as Scaffolds  
Synthetic scaffolds have better mechanical properties that can resist the transplantation procedure. Suitable bulk properties can be obtained in a controlled way by modifying the porosity, topographical parameters, and dimensional shape. Synthetic scaffolds are more advantageous than natural scaffolds because of their reproducibility and longer shelf life. Biocompatible, inert materials can be free from immunogenicity and their biodegradation rates can be manipulated. A number of polymers meet many of these requirements and have been approved by the food and drug administration (FDA) for an array of biodegradable suture applications including poly(lactic-co-glycolide acid) (PLGA), poly(l-lactic acid) (PLLA), PLLA-PLGA copolymer systems, poly(glycerol-sebacate) (PGS), polydimethylsiloxane (PDMS), polydimethylsiloxane (PDMS), poly(methyl methacrylate) (PMMA), poly(ethylene glycol) diacrylate (PEGDA), parylene-C and polycaprolactone (PCL). PLGA is a biodegradable polyester-based polymer having remarkable mechanical properties, adjustable degradation rates, and good processability [91]. It degrades by hydrolysis of ester linkages forming lactic and glycolic acids which are further degraded in the body. By varying the amount of lactic and glycolic acids, the degradation rate can be controlled. A clinical-grade PLGA scaffold was seeded with AMD patient-derived iPSC-RPE to demonstrate safety and cell integration in the eye [45]. This cell patch showed improved efficacy in rodent and porcine preclinical models. Concurrent PLGA scaffold degradation and ECM production by the donor cells aided integration with the host BM [45]. Biodegradable PCL scaffolds are the thinnest scaffolds available for retinal tissue engineering. This will act as a permeable and slowly degrading transient structure without any pathological increase in local acidity [92]. [PERSON] et al. [93] conducted _in vivo_ studies in rabbits to assess the tolerance and durability of micro and nanostructured PCL thin films. Adverse tissue responses like fibrosis or biodeposits were not observed and a good ocular tolerance was observed. Poly (trimethylene carbonate) (PTMC) is flexible and elastic in nature and a biodegradable polymer. In one of the studies, PTMC film was compared with an often-used biodegradable polymer namely poly (D, L-lactide) (PDLLA) film. The mechanical properties of PTMC film were found to be comparable to that of native Bruch's membrane (BM) and it also supported the formation of a functionally active hESC-RPE monolayer. On the other hand, PDLLA did not support the formation of hESC-RPE merging monolayers and had inappropriate mechanical properties when used for in vivo applications [94]. Synthetic polymers are generally hydrophobic in nature and usually not favorable for cell attachments. Oxygen-plasma processing, hydrogel blending and surface modifications such as coating surface with extracellular matrix proteins allow greater cell adhesion and survival. [PERSON] et al. [95] designed thin PMMA scaffolds of 6 um that were easy to implant and with reduced risk of trauma after transplantation into the rodent eyes. RPC on laminin-coated porous scaffolds resulted in increased cell survival and the delivery could be localized to specific retinal regions. [PERSON] et al. [96] generated a laminin-coated novel biodegradable nanowire PCL scaffold on which mouse RPCs were cultured. A microfabricated, elastic poly (glycerol sebacate) (PGS) scaffold was found suitable for initial RPC differentiation in vitro. Subretinal delivery into C57 bl/6 and rhodopsin knockout mice allowed the passage of nutrients and cells through its 50 um diameter pores. Polymer topology allowed photoreceptor maturation and migration of RPC into the retina demonstrating localized delivery of a predetermined number of cells to a specific region of the damaged retina. PGS has proved to be a potential scaffold for RPC delivery as indicated by high levels of survival, adherence, and proliferation [97]. [PERSON] et al.