Organic-inorganic dual-crosslinked hydrogel with extracellular matrix biomimetic and immune regulation for diabetic chronic wound healing.

To address delayed diabetic wound healing caused by persistent inflammation, an organic-inorganic dual-crosslinked hydrogel GelMA/DB (G/D) was fabricated using methacrylated gelatin (GelMA) and diatom biosilica (DB) to mimic the extracellular matrix (ECM) and modulate the wound immune microenvironment. The GelMA in G/D provides key characteristics of the extracellular matrix, including its functional composition, microstructure, and active sites. DB serves as a structural-functional unit in the GelMA network and improves the mechanical properties of the hydrogel. Through the combined effects of mechanical regulation and silicate ion release, G/D can modulate cell phenotypes, regulate the immune microenvironment, and promote tissue repair and regeneration. G/D containing 0.5% DB exhibited a compressive strength 3.2-fold higher than that of pure GelMA, while maintaining excellent injectability, tissue adhesion, and biodegradability. In vitro studies demonstrated that G/D reprogrammed the immune microenvironment by shifting macrophage polarization toward a reparative phenotype, via downregulation of TNF-α and IL-6 and upregulation of IL-10. Transcriptomic analysis further revealed that G/D activated multiple signaling pathways related to angiogenesis, energy metabolism, and extracellular matrix remodeling. In a diabetic rat wound model, G/D significantly accelerated wound closure, enhanced neovascularization, and guided ordered collagen deposition, ultimately regenerating skin tissue with near-normal structure and function. This study demonstrates that G/D promotes chronic wound repair through synergistic immune regulation and matrix remodeling, and proposes a simple, readily prepared wound dressing strategy with strong translational potential.