Naturally derived hydrogel with antioxidant, angiogenesis and photothermal effect to accelerate infected diabetic wound healing and reduce scar formation

<b>Rationale:</b> Diabetic wound treatment remains a central issue in global healthcare due to the unitary nature of clinical dressings, which lack systemic multifunctionality in terms of tissue adhesion, shape adaptation, hemostasis, antioxidant, anti-inflammatory and antimicrobial abilities and promotion of tissue repair. <b>Methods:</b> A hydrogel dressing loaded with active molecules of traditional Chinese medicine has been developed for the treatment of infected diabetic wounds. The naturally derived multifunctional hydrogel dressing (abbreviated as CTP) composed of Carboxymethyl chitosan (CMCS), 3,4,5-Trihydroxybenzaldehyde (THBA), and Phlorizin (PHL) was fabricated by a simple mixing process avoiding the use of any additional cross-linking agents or functional modifications. <b>Results:</b> The developed hydrogel demonstrated adhesiveness, shape adaptability, swelling, photothermal responsiveness, and other desirable biological functions, including hemostatic behavior and antibacterial, antioxidant and proangiogenic activities. In a diabetic wound model, compared with Hydrosorb Gel (a commercial hydrogel wound dressing), the CTP hydrogel in combination with NIR treatment accelerated diabetic wound healing by effectively preventing infection, decreasing inflammatory response, promoting re-epithelialization, enhancing both regeneration of skin attachments (e.g., hair follicles) and deposition of collagen. It also reduced scar formation and improved the overall healing process. <b>Conclusions:</b> As a functional wound dressing, CTP hydrogel shows great promise in diabetic wound repair.