Dual-crosslinked regenerative hydrogel for sutureless long-term repair of corneal defect

Corneal transplantation is the most effective clinical treatment for corneal defects, but it requires precise size of donor corneas, surgical sutures, and overcoming other technical challenges. Postoperative patients may suffer graft rejection and complications caused by sutures. Ophthalmic glues that can long-term integrate with the corneal tissue and effectively repair the focal corneal damage are highly desirable. Herein, a hybrid hydrogel consisting of porcine decellularized corneal stroma matrix (pDCSM) and methacrylated hyaluronic acid (HAMA) was developed through a non-competitive dual-crosslinking process. It can be directly filled into corneal defects with various shapes. More importantly, through formation of interpenetrating network and stable amide bonds between the hydrogel and adjacent tissue, the hydrogel manifested excellent adhesion properties to achieve suture-free repair. Meanwhile, the hybrid hydrogel not only preserved bioactive components from pDCSM, but also exhibited cornea-matching transparency, low swelling ratio, slow degradation, and enhanced mechanical properties, which was capable of withstanding superhigh intraocular pressure. The combinatorial hydrogel greatly improved the poor cell adhesion performance of HAMA, supported the viability, proliferation of corneal cells, and preservation of keratocyte phenotype. In a rabbit corneal stromal defect model, the experimental eyes treated with the hybrid hydrogel remained transparent and adhered intimately to the stroma bed with long-term retention, accelerated corneal re-epithelialization and wound healing. Giving the advantages of high bioactivity, low-cost, and good practicality, the dual-crosslinked hybrid hydrogel served effectively for long-term suture-free treatment and tissue regeneration after corneal defect.