In situ forming silk fibroin hydrogel dressing accelerates acute wound healing via immunomodulation and extracellular matrix regeneration.

Cutaneous injuries, a prevalent clinical challenge, often face delayed healing due to suboptimal wound management strategies. Conventional hydrogel dressings are limited by inadequate mechanical properties, poor bioactivity, and insufficient therapeutic efficacy. Here, we developed an innovative in situ forming hydrogel dressing by integrating silk fibroin (SF)-a natural biopolymer with tunable structural and bioactive properties-with polyvinyl butyral (PVB), which provides an ideal system for the delivery of active substances for wound healing and has broad application prospects in skin wound management. Upon ethanol evaporation, the SF/PVB composite rapidly formed a hydrogel film with enhanced mechanical strength, optimal breathability, and waterproofness. The SF-based dressing (LD-SF) demonstrated multifunctional wound-healing capabilities, including rapid hemostasis, antioxidative activity, and anti-inflammatory modulation. Notably, molecular-weight (MW)-dependent bioactivity was observed: low-MW SF (45 kDa) significantly promoted fibroblast proliferation and migration, while high-MW SF (72 kDa) exhibited superior immunomodulatory effects by polarizing macrophages toward pro-resolving phenotypes. In a murine full-thickness wound model, LD-SF accelerated re-epithelialization, enhanced angiogenesis, and stimulated collagen remodeling. Mechanistically, LD-SF facilitated extracellular matrix regeneration via β-sheet-driven structural stability and amino acid-mediated metabolic support. This dual-action system synergistically orchestrates immunomodulation-through macrophage phenotype regulation and cytokine balance-and robust extracellular matrix regeneration, offering a transformative approach to acute wound repair with minimized scarring and accelerated functional recovery. The study provides a clinically translatable solution for acute wound care by integrating rapid in situ film formation, molecular-weight-tunable bioactivity, and scar-minimizing outcomes, thereby addressing critical gaps in current wound management technologies.