Molecularly integrated dynamic chitosan network with topology-adaptive glucose/ROS responsiveness for coupled drug release and immunoregulation

Chronic diabetic wound exhibits persistent hyperglycemia-associated oxidative stress and unresolved inflammation, which together impair the transition from inflammatory to regenerative phases. In this study, we propose a topology-coupled molecular integration strategy to construct microenvironment-adaptive dynamic chitosan-derived microneedles for diabetic wound repair. Methacrylated chitosan was grafted with 4-formylphenylboronic acid and subsequently integrated with Astragaloside IV (AS) through reversible boronate ester and Schiff-base interactions, enabling the therapeutic molecule to function as a structural node within the dynamic network rather than a physically encapsulated payload. The resulting dual-crosslinked network combines permanent covalent stabilization with dynamic bond exchange, enabling structural adaptability. Under hyperglycemic and oxidative conditions, these dynamic linkages undergo bond exchange and partial dissociation, leading to network relaxation and accelerated drug release. The hydrogel exhibits enhanced viscoelasticity, stress relaxation capacity, and fatigue resistance, supporting robust microneedle penetration and sustained delivery. In vitro and in vivo studies demonstrate attenuation of AGEs accumulation, suppression of TLR4/NF-κB-mediated inflammation, promotion of M2 macrophage polarization, and enhancement of collagen remodeling and angiogenesis. These findings suggest that integrating bioactive molecules into dynamic polymer networks provides an effective strategy to couple material mechanics with immune regulation in diabetic wound repair.