Photocurable Dual-Network Hydrogels Based on Natural Polymers for Sutureless Repair of Large Corneal Defects

Abstract

Corneal transplantation remains the prevailing treatment for corneal defects, which is always restricted by donor shortages and numerous postoperative complications accompanying suturing. Photocurable hydrogels have emerged as alternative therapeutic strategies for the repair of corneal defects, but most hydrogels focus on repairing focal corneal defects and still suffer from low transparency and poor mechanical properties. Herein, photocurable hydrogel GelMA/OCS composed of gelatin methacryloyl (GelMA) and oxidized chondroitin sulfate (OCS) is developed for sutureless repair of large corneal defects (6 mm). This injectable hybridized hydrogel demonstrates excellent transparency, low swelling rate, enhanced mechanical properties, and superior adhesion properties. In vitro experiments reveal that GelMA/OCS hydrogel can support the proliferation and migration, and adhesion growth of human corneal epithelial cells (HCECs), demonstrating satisfactory cytocompatibility and cell affinity. In addition, GelMA/OCS hydrogel is capable of accurately filling the large corneal defects in rabbits and forming hydrogel grafts with smooth surfaces. Postoperative slit lamp, histological evaluation, and transcriptomic analysis reveal that GelMA/OCS hydrogel can significantly facilitate corneal re-epithelialization and the integration and reconstruction of stromal structures, as well as reduce inflammation responses and scar formation. Therefore, GelMA/OCS hydrogel may provide a promising alternative for the sutureless treatment of large corneal defects.