A Multifunctional Hydrogel Integrating Hemostatic, Antioxidant, and Antibacterial Properties for Infected and Diabetic Wound Regeneration.

Abstract

Wound management, especially for infected and diabetic ulcers, poses a persistent clinical challenge, largely attributed to sustained inflammation, bacterial colonization, and compromised tissue regeneration. Herein, a multifunctional hydrogel (CBOS) with integrated therapeutic properties was developed through Schiff base reaction between betaine-modified chitosan (CSBT) and oxidized sodium alginate (OSA), with poly(vinyl alcohol) and sodium borate incorporated to enhance network stability. The resulting CBOS hydrogel exhibited a uniform porous microstructure, robust viscoelasticity, high swelling capacity, and appropriate water vapor transmission. Comprehensive biocompatibility assessments confirmed its negligible cytotoxicity and applicable hemocompatibility. The hydrogel demonstrated broad-spectrum tissue adhesion and potent hemostatic efficacy in murine tail incision and liver hemorrhage models. Moreover, CBOS displayed antioxidant activity by scavenging multiple free radicals and reducing intracellular reactive oxygen species in H2O2-stressed fibroblasts. Antibacterial evaluations revealed potent activity against S. aureus, with molecular docking studies suggesting multitarget interactions with key bacterial proteins, including AgrA, ClpP, and FtsZ. In vitro, CBOS significantly enhances fibroblast migration. In vivo, the hydrogel accelerated healing in both S. aureus-infected full-thickness wounds and diabetic chronic wounds, as evidenced by reduced bacterial burden, attenuated inflammatory responses, enhanced collagen deposition, and promoted neovascularization. With its integrated hemostatic, antioxidant, antibacterial, and pro-regenerative properties, the CBOS hydrogel offers a viable and attractive therapeutic approach for complex wound tissue repair.