Self-healing and shape-adaptive nanocomposite hydrogels with anti-inflammatory, antioxidant, antibacterial activities and hemostasis for real-time visual regeneration of diabetic wounds

Diabetic severe wounds are difficult to heal and regenerate, and are extremely challenging to manage in clinical practice with common wound dressings. There is a need to develop multifunctional dressings that meet the requirements for efficient treatment of diabetic wounds. Therefore, the nanocomposite hydrogel with oxidized chondroitin sulfate (OCS), carboxymethyl chitosan (CMC), and phenol red-modified ε-poly-l-lysine (EPL-PR) as the backbones, encapsulated with chondroitin sulfate-modified selenium nanoparticles (CS@SeNPs) and infinite coordination polymer nanomedicine (ICPs) composed of procyanidins, berberine hydrochloride and Fe(III), was designed and fabricated. The prepared nanocomposite hydrogel system allows for rapid in situ gelation and complete coverage of irregular wounds. In vivo and in vitro investigations demonstrate that the nanocomposite hydrogel shows excellent tissue adhesion, antibacterial activities, biocompatibility and free radical scavenging properties. The rapid hemostasis of the nanocomposite hydrogel is confirmed through hemorrhage models of liver and caudal amputation. All the advantages enable the nanocomposite hydrogel to effectively induce skin tissue remodeling, promote vascular and hair follicle regeneration, remove free radicals from wounds, and accelerate wound healing. The nanocomposite hydrogel can also successfully monitor the pH range of 5–10, thus enabling real-time visual monitoring of the wound healing phase, facilitating wound management in clinical settings. This multifunctional wound dressing opens up ideas for the treatment and management of diabetic full-thickness wounds.