Dynamic injectable and multifunctional hydrogel incorporating dihydroquercetin (DHQ)-loaded chitosan nanoparticles for sustained DHQ release and accelerated burn wound healing

Burn wound healing is hindered by persistent inflammation, bacterial infection, and delayed tissue regeneration. Here, we developed DCNPs-Gel, an injectable, self-healing hydrogel incorporating dihydroquercetin (DHQ)-loaded chitosan nanoparticles (DCNPs; ~320 nm, PDI = 0.21, encapsulation efficiency 87.6%, drug loading 7.3%) into a dual-dynamic crosslinked oxidized sodium alginate (DO ~38%)/carboxymethyl chitosan network via Schiff-base and boronate ester bonds. DCNPs-Gel exhibited rapid self-healing (~96% modulus recovery within seconds), shear-thinning injectability (viscosity decreased ~3 orders of magnitude from 0.1 to 100 s −1 ), storage modulus ~830 Pa, high swelling ratio (1803%), and sustained DHQ release (~65% at 72 h). Bacteriostasis rates exceeded 90% against both E. coli (90.93%) and S. aureus (91.33%). Hemostatic evaluation demonstrated DCNPs-Gel reduced blood loss to ~200 mg versus ~580 mg (control) in the liver perforation model. In vitro , DCNPs-Gel maintained >90% HUVEC viability, reduced intracellular ROS by ~72%, and promoted scratch closure. In vivo , DCNPs-Gel accelerated deep second-degree scald wound closure to ~95.2% by day 18, enhanced collagen deposition and neovascularization. Mechanistically, DCNPs-Gel downregulated TLR4/NF-κB/IL-6/COX-2, upregulated VEGFA, rebalanced IL-6/IL-10 cytokine levels, and restored skin microbiota homeostasis. DCNPs-Gel uniquely integrates nanoparticle-mediated sustained release with dual-dynamic crosslinking, synergistically addressing oxidative stress, infection, hemostasis, and microbiota dysbiosis for comprehensive burn wound management.