Near complete corneal regeneration after lamellar keratoplasty in rabbits enabled by an in situ photo-crosslinkable dendrimer-hyaluronic acid hydrogel.

Abstract

PURPOSE: Corneal fibrosis is a leading cause of blindness that often requires corneal transplantation. However, transplantation is limited by donor shortages especially in low and middle-income countries, surgical complexity, and intensive postoperative management. We have developed an in situ photo-crosslinkable hydroxyl poly (amidoamine) [PAMAM] dendrimer-hyaluronic acid hydrogel (OcuPair) that produces 'near complete' regeneration of cornea regeneration, in approximately 6 months, in a rabbit keratoplasty model. METHODS: Sixteen rabbits (both male and female) were divided into two groups: anterior lamellar keratoplasty-shallow (ALK(S), n = 7) and anterior lamellar keratoplasty-deep (ALK(D), n = 9). Non-operated contralateral eyes served as controls. The hydrogel was applied after ALK(S) or ALK(D) surgery and then crosslinked with ultraviolet light. Corneal structure and re-epithelialization were assessed via anterior-segment optical coherence tomography (AS-OCT) and fluorescein staining at 14 and 28 days and 2, 3, 6, and 9 months. At 10 months, in vivo confocal microscopy (IVCM) imaging and histopathologic analyses were performed. RESULTS: By 6-10 months, near-complete corneal regeneration was observed, with ALK(S) and ALK(D) corneas achieving transparency comparable to that of healthy controls. AS-OCT and keratoscope data confirmed full epithelial repopulation, regenerated stroma, and near-normal anterior curvature. Histology and IVCM revealed restored corneal architecture with re-innervation of the epithelium and anterior stroma. CONCLUSION: OcuPair dendrimer-HA hydrogel provided mechanical support and promoted corneal regeneration after lamellar keratoplasty. It is a biocompatible scaffold for corneal repair, with significant promise as a viable alternative to conventional anterior lamellar keratoplasty.