# Tissue Engineering Strategies for Retina Regeneration
## 3 Tissue Engineering of the Retina  
The environment in which the cells grow and mature can influence their survival and functionality after transplantation. Tissue engineering of the retina is based on the concept that the transplantation of normal healthy cells derived from various stem cell sources needs to be implanted as an intact layer or sheet rather than injected as a suspension. Previously, subretinal delivery of cells through bolus injection has laid the groundwork and provided the \"proof of concept\" that healthy donor stem and progenitor cells can be transplanted into a diseased retina to contribute to visual functional recovery [70; 71]. These preclinical studies emphasized the requirement of improved cell delivery systems to enhance donor cell survival, integration, and neural connectivity.  
Advanced AMD is characterized by complete loss of PRs, dysfunctional RPE, and abnormal BM. BM is a 2-4 um thick extracellular matrix (ECM) composed of collagen types I and IV, laminin, fibronectin, hyaluronic acid, heparan sulfate chondroitin/dermatan sulfate, and elastin [72]. The specialized morphology of BM facilitates the reciprocal exchange of nutrients to and from the retina. In the diseased state, the BM show increased lipid body accumulation and a higher level of collagen cross-linking [73]. The degenerating RPE monolayer and its disrupted tight junctions further alter the BM morphology. These age-related changes result in decreased adhesion and survival of transplanted donor cells [12]. Several groups attempted to resurface BM to facilitate RPE attachment. Although coating the BM with a mixture of laminin, fibronectin, and vitronectin improved cell survival and phagocytosis of fluorescein isothiamate (FITC)-labeled bovine photoreceptor outer segments in both adult RPE and fetal RPE, the improvement was not comparable to healthy BM [74].  
Transplantation of healthy RPE/PR seeded in a carefully designed scaffold that can mimic the BM morphology and properties can better rescue the deteriorating visual function [9]. The central fovea has a neural retina thickness of 100 um whereas the BM is only 5 \(\upmu\)m [75]. In general, the ideal scaffold should be biocompatible, nonimmunogenic, and mechanically robust enough to resist manipulation during implantation. Scaffolds need to be thin enough to allow the exchange of nutrients and metabolites between the choriocapillaris and the retina [76]. After transplantation, it should not lead to physical distortion of the photoreceptor layer. Low elasticity of the material prevents adverse events like retinal detachment, retraction, or visual distortion. Carefully designed, cutting-edge biomaterials with fine-tuned topographical properties and micro/nanopatterned structures with extracellular matrix (ECM) properties can hold stem and progenitor cell populations effectively and help to deliver them as a retinal patch into the subretinal space.  
Different types of biomaterials have been used to design scaffolds for retinal tissue engineering. This includes natural polymers, synthetic polymers, hybrid polymers, decellularized tissues, and thermoresponsive hydrogel polymers.