Development of a biodegradable retinal cell graft for the treatment of retinal degenerative blindness

Abstract

BackgroundVision loss in inherited retinal diseases such as age‐related macular degeneration or retinitis pigmentosa result from death of the photoreceptor cells of the outer retina. Subretinal transplantation of induced pluripotent stem cell‐derived retinal progenitor cells (iPSC‐RPCs) has been found somewhat effective in restoring vision in blind animals, although survival of transplanted cells is poor. Polymeric support scaffolds have been shown to greatly enhance cellular survival and integration post‐transplantation, however attempts to materialize this concept have been largely unsuccessful for two reasons: 1) mechanical mis‐matching between material and the host retina and 2) improper cell packing. The goal of this study was to determine the ideal polymer fabrication parameters that promote optimal cell packing and biocompatibility.MethodsMethacrylate‐functionalized PCL scaffolds were polymerized with either Irgacure 651 or Irgacure 369 using two‐photon polymerization. Compressive modulus was measured using dynamic mechanical analysis. Four‐month‐old Yucatan mini pigs (n=10, 5 with Irgacure 651 and 5 with Irgacure 369) received 5mm diameter scaffolds containing iPSC‐RPCs via subretinal transplantation. Animals were examined clinically at 1 month post‐surgery and were subsequently sacrificed for histological analysis of the retina.ResultsPCL scaffolds were successfully generated using both photoinitiators. Scaffolds generated using Irgacure 651 cured rapidly and had a tendency to curl. Both Irgacure 651‐ and Irgacure 369‐generated scaffolds supported attachment and survival of human iPSC‐RPCs and both were successfully transplanted into the porcine subretinal space. At one month post‐transplantation, 50% of the retinas that received the Irgacure 651 scaffolds were attached. In the animals that received Irgacure 369 scaffolds all of the retinas reattached with no signs of ocular inflammation. In these animals retinal integrity, including maintenance of photoreceptor outer segments, was maintained.ConclusionPCL scaffolds support the maintenance of human iPSC‐RPCs and were biocompatible in the pig retina. These scaffolds may be ideal for retinal transplantation.Support or Funding InformationWynn Institute for Vision Research