Natural Extracellular Matrix Scaffold-Based Hydrogel Corneal Patch with Temperature and Light-Responsiveness for Penetrating Keratoplasty and Sutureless Stromal Defect Repair

Corneal transplantation remains the gold standard for treating corneal blindness; however, it is hampered globally by donor shortages and the complexity of suture-dependent procedures. Tissue-engineered corneas have demonstrated potential as corneal equivalents. Nevertheless, the development of adhesive corneal patches and full-thickness corneal substitutes remains challenging. In this study, a multifunctional hydrogel corneal patch (MHCP) is constructed by integrating a dual-crosslinked hybrid hydrogel with temperature and light responsiveness with a natural extracellular matrix scaffold. When applied to the ocular surface, MHCP spontaneously releases adhesives at body temperature and forms a stable adhesion with the recipient cornea through photocuring. In addition to its inherent mechanical, optical, and ultrastructural characteristics, which are similar to those of the natural stroma, MHCP demonstrates excellent suture resistance, anti-swelling, and anti-degradation properties after curing. MHCP promotes the proliferation and migration of corneal epithelial cells in vitro and maintains the phenotype of corneal stromal cells. In vivo, MHCP maintains graft hydration and restores corneal structural integrity and transparency during penetrating keratoplasty of various sizes and sutureless lamellar keratoplasty. Collectively, given the advantages of native stroma-like characteristics, operation-facilitating multiple functions, and convenient preparation, MHCP is a promising corneal substitute for clinical applications.