Dual crosslinked thermosensitive hydrogel engineered with multiple dynamic hydrogen bonds for enhanced photodynamic antibacterial activity and wound healing.

Abstract

To address the challenges posed by bacterial infection and the persistent oxidative microenvironment in diabetic wounds, a multifunctional intelligent hydrogel dressing (SPC) was developed, comprising sodium alginate (SA) , poly (N-isopropylacrylamide) (PNIPAM) , and an encapsulated photosensitizer. This hydrogel features a dual-crosslinked network and supported by hydrogen bond relay system. The results demonstrate that SPC exhibits unique thermosensitivity, with its lower critical solution temperature (LCST) precisely regulated to 26.8 °C through hydrogen bonding. This thermoresponsive behavior enables spontaneous contraction at body temperature, generating mechanical forces that promote wound closure. The hydrogel exhibits outstanding broad-spectrum antibacterial activity, achieving bactericidal efficiencies of 99.63% and 98.95% against MRSA and ESBL E.coli, respectively, and a 94.3% inhibition rate against MRSA biofilms under light irradiation. This enhanced antibacterial performance is attributed to a narrowed bandgap (ΔEg) and the formation of a hydrophobic microenvironment by PNIPAM, which together promote C3AC, aggregation, and significantly elevate ROS generation. Notably, the hydrogel exhibits significant antioxidant activity, efficiently scavenging excessive ROS to alleviate oxidative stress. This capability synergizes with its immunomodulatory function of regulating macrophage polarization by downregulating the pro-inflammatory M1 phenotype and upregulating the anti-inflammatory M2 phenotype, thereby comprehensively remodeling the wound microenvironment and promoting tissue regeneration. In vivo evaluations confirmed that SPC significantly accelerates the healing of infected wounds, achieving a 94.1% closure within 14 days, while enhancing collagen deposition, angiogenesis, and M2 macrophage polarization. STATEMENT OF SIGNIFICANCE: We present a dynamic "hydrogen-bonded relay" hydrogel dressing, synthesized from temperature-responsive poly (N-isopropylacrylamide) , a coumarin-based photosensitizer (C3AC) , and biocompatible sodium alginate, which functions as a "Dual-Engine" system to synergistically accelerate the healing of infected diabetic wounds. Unlike conventional passive hydrogels, our material uniquely combines thermo-mechanical-autonomous contraction with enhanced photodynamic antibacterial activity. The dynamic hydrogen-bond network among these components not only fine-tunes the phase transition to body temperature for effective wound closure but also creates a hydrophobic microenvironment that promotes photosensitizer aggregation and dramatically boosts reactive oxygen species generation. This leads to exceptional antibacterial efficacy against drug-resistant strains and robust anti-biofilm performance. Furthermore, the hydrogel actively modulates macrophage polarization to resolve inflammation and promotes collagen deposition and angiogenesis. This work provides an innovative design strategy for intelligent, multifunctional wound dressings with broad implications for regenerative medicine.