Self-Adaptive Biomimetic Nanocomposite Hydrogel Orchestrates Dual-Targeting and On-Demand H2S Gasotransmission for Multifactorial Diabetic Wound Therapy.

Diabetic wounds remain a persistent clinical challenge due to the intertwined pathologies of chronic inflammation, oxidative stress, bacterial colonization, and impaired neovascularization. Conventional hydrogel dressings, however, typically lack both the spatiotemporal precision and synergistic multifunctionality that are required to counteract the complex pathological drivers of diabetic wound chronicity. Here, we present a biomimetic nanocomposite hydrogel (QN-S-HG) that integrates neutrophil-membrane-coated quercetin-loaded nanoparticles with a pH-responsive hydrogen sulfide (H2S) releasing hyaluronic acid network. The neutrophil-mimetic nanoparticles achieve dual-targeted delivery to inflammatory cells and bacteria, simultaneously exerting anti-inflammatory, antioxidant, and broad-spectrum antibacterial effects. Concurrently, the H2S donor S-propargylcysteine (SPRC) is covalently conjugated via dynamic Schiff base bonds to the hydrogel scaffold, enabling acid-triggered release in the pathological wound milieu to stimulate angiogenesis. Remarkably, the crosslinker-free and hydrogen-bond-mediated hyaluronic acid network endows the hydrogel with injectability, self-healing, and tissue-adhesive properties, ensuring conformal coverage and sustained local bioactivity. In a diabetic rat full-thickness wound model, QN-S-HG markedly accelerates closure, promotes macrophage repolarization, enhances neovascularization, and facilitates orderly collagen remodeling with hair follicle regeneration. By orchestrating targeted pharmacotherapy, microenvironment-triggered gaseous signaling, and adaptive material mechanics, this platform addresses the multifaceted pathophysiology of diabetic wounds and offers a clinically translatable paradigm for advanced regenerative wound care.