Near-infrared light-responsive multifunctional hydrogel releasing peptide-functionalized gold nanorods sequentially for diabetic wound healing

Treatment for chronic diabetic wounds remains a clinical challenge. Wound healing process occurs in three phases: inflammation, proliferation and remodeling. Several factors including bacterial infection, decreased local angiogenesis and diminished blood supply delay wound healing. There is an urgent need to develop wound dressings with multiple biological effects for different stages of diabetic wound healing. Here, we develop a multifunctional hydrogel with two-stage sequential release upon near-infrared (NIR) stimulation, antibacterial activity and pro-angiogenic efficacy. This hydrogel consists of covalently crosslinked bilayer structure, with the lower thermoresponsive poly(N-isopropylacrylamide)/gelatin methacrylate (NG) layer and the upper highly stretchable alginate/polyacrylamide (AP) layer embedding different peptide-functionalized gold nanorods (AuNRs) in each layer. Antimicrobial peptide-functionalized AuNRs released from NG layer exert antibacterial effects. After NIR irradiation, the photothermal transition efficacy of AuNRs synergistically enhances bactericidal efficacy. The contraction of thermoresponsive layer also promotes the release of embedded cargos during early stage. The pro-angiogenic peptide-functionalized AuNRs released from AP layer promote angiogenesis and collagen deposition by accelerating fibroblast and endothelial cell proliferation, migration and tube formation during the subsequent healing phases. Therefore, the multifunctional hydrogel with effective antibacterial activity, pro-angiogenic efficacy and sequential release behaviors is a potential biomaterial for diabetic chronic wound healing.