Engineered near-infrared-responsive PNIPAM/alginate hydrogels for active mechanical stimulation and infection control in diabetic wound healing.

Abstract

Diabetic wound healing is severely impaired by four core pathological barriers-persistent hyperglycemia, excessive inflammation, bacterial infection, and deficient wound contraction. Herein, we developed a near-infrared (NIR)-responsive antibacterial hydrogel composed of poly(N-isopropylacrylamide), sodium alginate, graphene oxide, and tetracycline hydrochloride (PNIPAM/Alg/GO/TH), in which chitosan serves as an interfacial bridging component that covalently and electrostatically anchors the hydrogel to tissue rather than acting as a bulk matrix constituent. As a natural polysaccharide, sodium alginate serves as the essential hydrogel matrix, endowing the system with high water retention, biocompatibility, and a porous network favorable for exudate absorption and tissue regeneration, while also forming a mechanically robust double-network structure with PNIPAM. Through chitosan-mediated interfacial bioadhesion, the hydrogel firmly adheres to wound tissues, enabling transfer of the contraction force to the wound edges. Under NIR irradiation, the hydrogel exhibited potent broad-spectrum antibacterial activity, with bactericidal rates of 98.5 ± 0.53% against Staphylococcus aureus and 99.25 ± 0.75% against Escherichia coli. Meanwhile, NIR stimulation induced a phase transition and active mechanical contraction, promoting centripetal wound closure, while the photothermal effect triggered sustained tetracycline release for prolonged antimicrobial protection. In vivo, in a Staphylococcus aureus-infected diabetic mouse wound model, the hydrogel significantly downregulated inflammatory markers and promoted neovascularization and collagen deposition, achieving a wound healing rate of 94.75 ± 2.09% on day 10. This study presents a sodium alginate-based interfacial hydrogel strategy that integrates interfacial adhesion, active mechanical contraction, and on-demand drug delivery for rapid diabetic wound healing.