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.