Artificial Cornea Substitute Based on Hydrogel Skeletons with Natural Stromal Hierarchical Structure and Extracellular Matrix for Sutureless Transplantation

Corneal substitutes with structural and compositional characteristics resembling those of natural corneas have attracted considerable attention. However, biomimicking the complex hierarchical organization of corneal stroma is challenging. In this study, humanized corneal stroma-like adhesive patches (HCSPs) are prepared through a multi-step process. First, polyethylene glycol diacrylate is cast and cured within decellularized porcine cornea (DPC) templates. The DPCs are then enzymatically digested to obtain hydrogel skeletons, which are finally integrated with human corneal extracellular matrix and methacrylate gelatin. HCSPs replicate the ultrastructure, protein components, and optical properties of human corneas and exhibit improved anti-swelling and anti-degradation capabilities compared with conventional DPCs and recombinant human collagen patches. HCSPs can deliver methacrylate gelatin at the ocular surface temperature (37 °C) and achieve stable adhesion to the corneal stroma upon 405 nm light irradiation. Furthermore, HCSPs promote the survival and migration of corneal epithelial and stromal cells while preserving their phenotypes. In rabbit models of lamellar keratoplasty and microperforation repair, HCSPs accelerate epithelial healing, minimize suture-associated complications, and maintain structural stability. These findings suggest that HCSPs are promising donor corneal substitutes for clinical applications.