Tunable and Saline-Responsive SA-CS-PAM Hydrogel for Adaptive Wound Dressing and Localized Drug Delivery Management

Chronic and burn wounds demand dressings that combine secure atraumatic adhesion, exudate management, mechanical resilience, and on-site therapy. We engineered a multifunctional hydrogel comprising sodium alginate (SA), chitosan (CS), and polyacrylamide (PAM) through dual physical-chemical cross-linking. The material displays saline-triggered reversibility of adhesion, programmable swelling (≈200% in the hydrated state and up to ≈3000% after lyophilization), and sustained drug release. Among tested formulations, 10% PAM offered the best mechanical properties (tensile strength 99.12 ± 5.43 kPa; elongation at break >2500%) and viscoelastic balance. The hydrogel maintained robust adhesion to soft tissues and detached within ∼5 s upon 0.9% NaCl irrigation, allowing for gentle and rapid removal (The adhesion strength of the 10% hydrogel decreased by about 45%). Shikonin-loaded gels achieved 83.44 ± 1.53% cumulative release within 12 h. Hydrogel extracts were noncytotoxic and promoted L929 and NIH/3T3 fibroblast proliferation and migration. Flow cytometry and transcriptomic analyses showed accelerated G1→S progression and enrichment of DNA replication/repair pathways, with activation of JAK-STAT signaling. In full-thickness and deep partial-thickness burn models, hydrogels accelerated closure, improved re-epithelialization, enhanced collagen organization and neovascularization, and lowered inflammatory cytokines, all without systemic toxicity. Notably, the saline-triggered detachment leverages standard clinical irrigation procedures, underscoring the translational potential. These results support SA-CS-PAM hydrogels as clinically adaptable dressings that enable atraumatic removal, exudate-adaptive swelling, and local drug release for improved wound repair.