“one stone four birds” strategy of advanced hydrogel system based on eight-arm nanocages to promote chronic wound healing in diabetes

Due to the frequent occurrence of microvascular impairments and persistent bacterial infections in wounds of diabetic patients, the resulting hindered wound healing process presents a formidable challenge in clinical management. In this study, an advanced multifunctional hydrogel system was developed to promote chronic diabetic wound healing, which is made from a combination of a biopolymer hydrogel with eight-arm nanocages crosslinking and an adhesive layer in the form of fibrous membranes. This system can conveniently adhere to wet and dynamic tissue surfaces and form a protective barrier covering the wound site in a timely manner to provide the necessary healing conditions for chronic diabetic wounds. Through a synergistic combination of the hydrogel network and quaternized nanocages, the hydrogel system exhibited excellent antimicrobial properties. In addition, the nanocages crosslinking network functioned as the rigid framework to restrict the excessive swelling of the biopolymer hydrogel matrix, which avoided affecting wound healing. Owing to the hydrogel comprising a thermoresponsive polymer network, the dressing system could actively contract wounds after tough adherence to the tissue in response to the temperature of the physiological environment. The combined hydrogel incorporating a nanocage network and thermoresponsive polymer endows the hydrogel system with a useful drug delivery carrier for the sustained release of exosomes to promote angiogenesis in chronic wounds. The integration of excellent antimicrobial activities, strong tissue adhesion property, desirable mechanically active contraction and controlled release in this advanced multifunctional hydrogel system makes it possible to develop an ideal wound dressing, which is effective for promoting diabetic wound healing.