## 3 Tissue Engineering Approach
### Conventional Fabrication Techniques
The findings of this study indicated that fibrin hydrogels could be easily manipulated with surgical tools and degraded rapidly into products recognized and metabolized by the body. IPSC-RPE cells on a fibrin hydrogel were viable and organized into a functional monolayer that could be preserved during and after implantation thanks to the hydrogel support [66]. However, despite their high biocompatibility, hydrogels have low mechanical properties and, hence, they are not suitable as a [PERSON]'s membrane substitute. In fact, hydrogel stiffness ranges from a few Pa to few kPa whereas the elastic modulus of [PERSON]'s membrane is estimated to be around few MPa [5]. Hydrogels were also employed as 3D scaffolds for neural retina tissue engineering to regenerate damaged photoreceptors and RGCs [69; 70]. Conjunctiva stem cells encapsulated in fibrin gels differentiated into photoreceptor-like cells, thus providing a new potential therapy for diseases involving photoreceptor injuries [70]. Similarly, retinal ganglion-like cells were differentiated from dental pulp stem cells suspended in fibrin gels [69]. This construct could be transplanted into patients with glaucoma to repair axonal damage and prevent further RGC death. The 3D networks resembled the physiological 3D microenvironment of the neural retina, thus promoting cell viability, differentiation and function when compared with 2D cultures [68; 69; 70]. However, the molding fabrication method has a limited microarchitecture and cell distribution controllability. Another technique that has been explored in retinal tissue engineering is thermally induced phase separation (TIPS). TIPS induces the destabilization of a homogenous solution composed of a polymer dissolved in a solvent [71]. After dissolution, a polymer can be thermodynamically unstable at low temperatures, thus causing a spontaneous separation of the solution into a polymer-rich phase and a solvent-rich phase. Lowering the temperature in a controlled manner causes the solidification of the solvent and subsequently the separation of the polymer from the solvent. The solvent crystals are then removed through extraction, evaporation and sublimation resulting in porous structures [72]. The TIPS method has been largely employed for tissue engineering applications in general, for example, bones and cartilage, due to its ability to produce highly porous scaffolds with interconnected pores [73; 74; 75]. Porous membranes, fabricated by a separation phase, were investigated as a scaffold for RPE transplantation [76]. TIPS was also used to fabricate scaffolds for retinal progenitor cells isolated from mice eyes [77]. Seeded scaffolds were tested in vitro and then implanted into models of retinal degeneration. The outcomes of this study indicated that the scaffolds promoted cell differentiation in vitro and cell survival in vivo [77]. The guidance of cell differentiation by the substrate could be exploited to form functional photoreceptors to replace the cells lost due to degenerative diseases. However, the use of the TIPS technique is limited by the low control of pore size and geometry [73]. The retinal scaffolds produced by conventional techniques are listed in Table 1. Due to their own limits, the conventional fabrication methods have been mostly replaced by innovative techniques that hold great promise as potential treatments for retinal degenerative diseases.