Photocontrolled Bionic Micro‐Nano Hydrogel System used Novel Functional Strategy for Cell Delivery and Large‐Scale Corneal Repair

Abstract Reproducing the microstructure of the natural cornea remains a significant challenge in achieving the mechanical and biological functionality of artificial corneas. Therefore, the development of cascade structures that mimic the natural extracellular matrix (ECM), achieving both macro‐stability and micro‐structure, is of critical importance. This study proposes a novel, efficient, and general photo‐functionalization strategy for modifying natural biomaterials. Collagen microfibers obtained through electrospinning are functionalized with an active N‐Hydroxysuccinimide (NHS) ester, to impart light‐curing ability. This approach expands the construction of photo‐controllable hydrogel systems beyond conventional single methacrylate (MA) modifications or di‐tyrosine bonding, enabling integration with other biomaterials for comprehensive ECM remodeling. Subsequently, the collagen microfibers are then photo‐embedded into gelatin methacryloyl (GelMA) via covalent crosslinking to form a fibrous hydrogel, which supports both structural and functional requirements. In terms of biological functionality, the hydrogel promotes significant inward migration and retention of human corneal fibroblasts (hCFs), replicating ECM‐like environments. Furthermore, its excellent burst resistance suggests potential as a bioadhesive. In a rabbit model, the hydrogel achieved effective repair of large‐sized (6 mm) corneal defects, facilitates epithelial migration, and maintained long‐term stability. This work provides valuable guidance for designing efficient and simplified bioactive materials for corneal repair and broader tissue engineering applications.