## 3 Tissue Engineering Approach
### Electrosppinning  
The electrospinning process has been suggested as a promising technique to fabricate a prosthetic Bruch's membrane as it is able to recapitulate the nanofibrous structure of a native Bruch's membrane [78]. Indeed, the electrospinning technique is able to produce 3D thin nanofibrous membranes by using natural and synthetic polymers [79]. These fibrillar networks are highly permeable for solutes, thus facilitating cell adhesion and proliferation [79]. The electrospinning setup involves a high-voltage supply, a capillary tube/syringe with a needle, a syringe pump and a collector. The high-voltage supply applies a positive charge to a polymeric solution (solution electrospinning) or melt (melt electrospinning) that is extruded from the needle forming a jet. The jet becomes unstable and thin and forms fibers while the solvent evaporates. The fibers are deposited onto a collector [80]. The morphological properties of electrospun membranes such as thickness, fiber size and orientation can be tuned simply by changing the specific parameters of the electrospinning process such as the polymer concentration, solution flow rate and collector distance [81]. Many studies have reported the fabrication of electrospun scaffolds for vascular, cardiac and neural tissue engineering [82; 83; 84]. Solution electrospinning has been utilized to produce a prosthetic Bruch's membrane to engineer an RPE layer. The hypothesis is that the RPE monolayer engineered on thin electrospun membranes could become an effective therapy to cure blindness and the deficiencies associated with RPE and Bruch's membrane degeneration. Synthetic and natural polymers including poly(lactic acid) (PLA), poly(\(\varepsilon\)-caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA), silk fibroin and silk fibroin-PCL-gelatin were used to fabricate electrospun Bruch's membrane-like scaffolds [85; 86; 87; 88; 89; 90; 100]. Typically, a blend of natural and synthetic materials is electrospun as synthetic polymers exhibit good mechanical properties and a controlled degradation rate while pure naturally-derived polymers promote cell adhesion and proliferation. [PERSON] et al. successfully produced ultrathin nanofibrous scaffolds based on collagen and PLGA that closely imitated the structure of a native Bruch's membrane [85]. Human RPE cells seeded onto these scaffolds formed a functional monolayer with a typical cobblestone morphology and abundant sheet-like microvilli on their apical surfaces; however, no results of the scaffold mechanics and permeability were reported [85]. In our previous paper, we fabricated a Bruch's membrane-like membrane composed of a blend of _Bombyx mori_ silk fibroin and PCL to study the pathological mechanisms of AMD in a 3D in vitro model [100]. The resulting scaffolds showed similarities with a human Bruch's membrane with regard to the architecture, permeability and mechanical properties [100]. These in vitro studies indicated the feasibility of using electrospun membranes as a prosthetic Bruch's membrane on which a functional RPE monolayer is formed. As such, RPE patches, composed of electrospun scaffolds previously seeded with RPE cells, have been investigated in vivo. The RPE patches were proven to be biocompatible when implanted in animal models showing no adverse reactions [86; 89; 92; 95; 98]. [PERSON] et al. also evaluated the functionality of clinical-grade iPSC-RPE patches in rats and in a porcine laser-injured model. According to the findings, the use of the scaffold improved the patch integration and efficacy over the cell suspension [95]. In fact, an increased photoreceptor preservation was encountered in animals transplanted with the patch in respect to those injected with the cell suspension. This study has led to a phase I/II clinical trial (NCT04339764) based on patch subretinal transplantation in patients suffering from advanced stages of dry AMD.