# Tissue Engineering Strategies for Retina Regeneration
## 5 Other Complex Tissue Engineering Approaches  
Drop casting [120], solvent casting [120], electrospinning [113], soft lithography [120], and microfabrication [97] are some of the techniques conventionally used to produce scaffolds for retinal repair. These methods can be used to fabricate porous scaffolds. The pore size and porosity can be controlled by choosing the correct particle size and the right number of added particles. The robotic deposition is an upcoming technology in tissue engineering for computerized and reproducible patterning of ultrathin membranes for cell delivery [115]. This will allow controlled cellular deposition in micrometer levels. Cell adhering surfaces can be manipulated to tailor the alignment and morphology of the attached cells through the introduction of cell-aligning grooves. The viable cells are delivered through a bio-ink which consists of a biocompatible polymer [121]. In 3D bioprinting, the components are fabricated by layers directly from a computer-assisted design file [120]. 3D bioprinting allows combining cells, biomaterials, and growth factors to mimic the natural tissue characteristics. Conventional methods lack precision and  
Figure 3: Tissue- engineered RPE-Retinal organoid co-graft transplantation into subretinal space of RCS rats (**a**) schematic representation, showing the transplantation of RPE-RO cograft into the degenerated retina. After transplantation to the subretinal space, both pieces integrate to repair a damaged retina. GCL: ganglion cell layer, IPL: inner plexiform, INL: inner nuclear, OPL: outer plexiform, ONL: outer nuclear, OS: outer segments, RPE: retinal pigment epithelium, BM: basement membrane. (**b**) Immunohistochemical staining showing RPE-RO co-graft integration into the degenerative rat retina, 3 months post-implantation. (**i**) in (**b**) co-graft (red nuclei) in subretinal space of rat. The transplant has developed rosettes. White arrows: migrated donor cells in the host (**ii**) in (**b**) bestrophin (green) shows donor RPE (red arrows) and host RPE (blue arrows). (**c**) Ultrasound images after ROE-RO cograft transplantation. (**i**) in (**c**) ultrasound image of a co-graft observed during fundus examination of RCS rat- 3 months post-implantation) (**ii**) in (**c**) vertical OCT B-scan image passing through the transplant area. Blue arrow: RPE layer on synthetic Bruch’s membrane, white arrow: organoid layer above RPE. Here the RPE-RO co-graft area appears like a normal retina whereas the outside area (indicated by the red arrow) shows considerable loss of retinal thickness. (**iii**) in (**c**) Vertical OCT B-scan image of another RPE-RO cograft transplant at 5 months post-surgery (unpublished data).  
the ability to create constructs having complex designs. Since the structure of the retina is complex with a heterogeneous cell population and degenerative diseases affecting photoreceptors, RPE, choriocapillaris, and BM; 3D bioprinting technology can be applied to repair the damaged retinal layers. Using 3D bioprinting, [PERSON] et al. printed a retina model composed of a PCL ultrathin membrane, Y79 cell-laden alginate/pluronic bio-ink, and ARPE-19 cell monolayer with potential applications in drug delivery, disease mechanism, and treatment method discoveries [122]. In another study, to develop an in vitro retina model, an inkjet bioprinting system was applied to PR cell layers placed on top of bioprinted RPE. Results showed well-positioned layered structures expressing their structural markers. Human vascular endothelial growth factors were released from RPE printed layer confirming a functional RPE monolayer obtained by bioprinting [123].