Fast and versatile ice-template-assisted photocrosslinking of methacryloylated gelatin-based nanofiber sponges for regenerative wound healing

Fast ITAP enables nanofiber sponge crosslinking with low GelMA content. • ITAP reduces crosslinking time by ∼10-fold versus GA-mediated methods. • ITAP preserves the ECM-mimicking porous fibrous architecture. • The nanofiber sponge shows high wettability, water uptake, and wet stability. • The nanofiber sponge exhibits low cytotoxicity and promotes wound healing. Nanofiber sponges have emerged as promising materials for regenerative wound healing, yet their fabrication remains constrained by the use of conventional chemical crosslinkers. Herein, we report a fast ice-template-assisted photocrosslinking (ITAP) strategy for constructing methacryloylated gelatin (GelMA)-based nanofiber sponges. By coupling ice templating with photocrosslinking, this strategy drives the preferential enrichment and in situ fixation of a small amount of GelMA around nanofiber junctions, thereby enabling effective bonding between fibers while preserving the highly porous fibrous architecture resembling the native extracellular matrix. As a result, the crosslinking process is completed within only 3 min, representing an approximately 10-fold reduction in crosslinking time compared with conventional methods mediated by glutaraldehyde. The resulting GelMA-based nanofiber sponge exhibits high porosity (98.2%), superhydrophilicity, high water uptake (∼4500%), compliant mechanical properties, and excellent structural stability under hydrated conditions. Moreover, it shows low cytotoxicity (95% cell viability) and promotes wound repair in a full-thickness skin defect model, including attenuated early inflammatory response, enhanced early CD31-positive response associated with angiogenesis, and organized collagen remodeling with a reduced collagen I/III ratio, ultimately leading to accelerated wound closure (91.47% by day 13) and improved skin repair. In addition, preliminary extension experiments using methacryloylated alginate (AlgMA) and methacryloylated chitosan (ChiMA) suggest the potential applicability of the ITAP strategy to other methacrylated biopolymers. This work establishes an efficient strategy for constructing biocompatible GelMA-based nanofiber sponges and highlights their potential for regenerative wound healing.