Multifunctional gelatin/phycocyanin composite hydrogel for infected wound therapy: pH-responsive drug release,...

Infected wound healing remains a critical challenge in clinical practice, necessitating advanced therapeutic strategies. This study developed multifunctional gelatin/phycocyanin (Gel/PC) composite hydrogels (GP) via EDC/NHS-activated amidation and THPS-mediated Mannich reaction. By systematically varying Gel, THPS, and PC concentrations, an optimal formulation (GP1: 20 % Gel, 0.4 % THPS, 1 % PC) was identified. GP1 exhibited a uniform porous microstructure, rapid gelation (~650 s), pH-responsive swelling, superior mechanical strength (fracture energy ~6.03 MJ/m³), excellent self-healing capacity, and strong tissue adhesion. The hydrogel demonstrated significant antioxidant activity (>80 % DPPH scavenging) and potent antibacterial effects against S. aureus (99.09 % inhibition) and E. coli (97.32 % inhibition). Loaded with polydeoxyribonucleotide (PDRN), the GPP hydrogel showed pH-responsive release with near-complete drug delivery (99.9 %) at wound pH (5.5). In a rat full-thickness wound model, GPP treatment achieved 81.34 % wound closure within 10 days, promoted re-epithelialization, enhanced collagen deposition (71.23 % area), attenuated inflammation (reduced IL-6 and TNF-α), and stimulated angiogenesis (increased VEGF). These results indicate that the GP hydrogel is a promising therapeutic platform for infected wounds.