Fabrication of Mechanically Adjustable Silk Fibroin-Based Hydrogels with Excellent Biocompatibility for Skin Wound...

Silk fibroin (SF) hydrogels have attracted widespread attention as promising wound dressings owing to their excellent biocompatibility and tunable structure. However, constructing SF hydrogels with easily adjustable mechanical properties and clarified structure-function relationships remains challenging. Herein, we fabricated a series of mechanically tunable SF hydrogels using ethylene glycol diglycidyl ether (EGDE) as a biocompatible crosslinker. The epoxy groups of EGDE readily react with the nucleophilic amino and hydroxyl groups on SF chains via ring-opening reactions, forming stable covalent crosslinks. By systematically optimizing the SF concentration, crosslinker molar ratio, and reaction temperature, hydrogels with well-defined porous architectures, stable crosslinked networks, and favorable biosafety were obtained. Among them, the 150-90-1 hydrogel exhibited optimal comprehensive performance, with a compressive strength of ∼250 kPa, a tensile strength of ∼280 kPa, and an adhesion strength of ∼4.5 kPa to porcine skin. In vitro results confirmed that the hydrogel had cell viability above 90% and supported cell survival and proliferation. In vivo experiments using a mouse full-thickness skin wound model demonstrated that the hydrogel significantly accelerated wound closure, attenuated inflammatory infiltration, promoted re-epithelialization and collagen deposition, and enhanced angiogenesis by upregulating VEGF (28% at day 3; 47.8% at day 12) and CD31 (14.5% at day 3; 24.5% at day 12) while downregulating IL-6. Mechanistically, the negatively charged SF backbone enriched the positively charged endogenous VEGF through electrostatic interactions, and the hydrogel acted as a protective physical barrier to maintain a stable wound microenvironment. This work provides a facile strategy for developing mechanically adjustable SF hydrogels and elucidates their regulatory mechanism in wound repair, highlighting their great potential as safe and effective wound dressings.