A natural corneal extracellular matrix-inspired dual-crosslinked hydrogel bioadhesive for emergency corneal trauma repair

Emergency corneal injuries necessitate immediate intervention to minimize the risk of infection and maintain optical clarity. However, corneal transplantation is unsuitable due to donor shortage and surgical complexity. Inspired by the synergistic role of collagen and glycosaminoglycans in the natural cornea extracellular matrix, a visible light-initiated, in situ dual-crosslinked hydrogel bioadhesive (GelMA-CSMA-NHS) is prepared by combining gelatin methacryloyl (GelMA) and N-hydroxysuccinimide-modified chondroitin sulfate methacrylate (CSMA-NHS). Upon exposure to 405 nm light, the bioadhesive precursor rapidly forms a hydrogel within 3 min directly on the injured cornea. It establishes strong interfacial integration with the tissue through topological entanglement and NHS-amine covalent crosslinking, thereby serving as a suture-free alternative for corneal repair. The dual-crosslinking mechanism significantly enhances the mechanical cohesion of the hydrogel, which synergistically improves its adhesive performance. The resulting hydrogel demonstrates high transparency, stable swelling behavior, good biocompatibility and biodegradability, and high burst pressure resistance. Using established models of partial stromal defects and full-thickness corneal lacerations, the bioadhesive integration and pro-healing effects of the hydrogel were evaluated. The results showed that the hydrogel bioadhesive rapidly seals corneal wounds, promotes re-epithelialization, reduces scarring formation, and supports full-thickness corneal regeneration. STATEMENT OF SIGNIFICANCE: To address the limitations of traditional surgical sutures in treating acute corneal injuries, we developed a hydrogel bioadhesive (GelMA-CSMA-NHS). Inspired by the composition of the natural corneal extracellular matrix, the adhesive is fabricated from two derivatives of natural bioactive macromolecules. It can be rapidly crosslinked in situ on the injured cornea under visible light initiation via a dual-crosslinking mechanism, forming a strong adhesive interface with the tissue through topological entanglement and NHS-amine covalent bonding. In terms of performance, the hydrogel bioadhesive exhibits high transparency, good biocompatibility and biodegradability, and high burst pressure resistance. The hydrogel was evaluated in two models of acute corneal injury-partial stromal defects and full-thickness corneal lacerations. It accelerates re-epithelialization, minimizes scarring formation, and supports full-thickness corneal regeneration. Thus, this hydrogel bioadhesive shows considerable potential for emergency corneal repair and regenerative medicine.