Double-network PVA/γ-PGA/fucoidan hydrogels with favourable biocompatibility and anti-inflammatory activity for wound healing.

Acute wound healing still faces numerous challenges, such as excessive inflammatory response, prolonged hemostasis time, and insufficient tissue regeneration, which often lead to delayed wound healing and scar formation. To address these issues, this study developed a multifunctional "physical-ionic" dual-network hydrogel (PPF hydrogel). This hydrogel combines an elastic polyvinyl alcohol (PVA) scaffold with a rigid ionic network composed of γ-polyglutamic acid (γ-PGA) and fucoidan, cross-linked via Ca2+. The resulting hydrogel possesses a highly interconnected porous structure, exhibiting excellent mechanical strength and moderate tissue adhesion. In vitro and in vivo evaluations showed that the PPF hydrogel has good blood and cell compatibility, rapidly achieving hemostasis and promoting the proliferation and migration of L929 fibroblasts. In a mouse full-thickness skin resection model, the PPF significantly accelerated wound closure while reducing epidermal hyperplasia and promoting orderly collagen deposition. Mechanistically, the PPF effectively modulates the immune microenvironment by downregulating pro-inflammatory cytokines (TNF-α, IL-6) and upregulating anti-inflammatory factors (IL-10) and VEGF. This regulation promotes M2 macrophage polarization and angiogenesis, thereby accelerating the transition from the inflammatory phase to the remodeling phase. This dual-network hydrogel offers a promising therapeutic strategy for high-quality acute wound repair in regenerative medicine.