NIR/glucose stimuli-responsive multifunctional smart hydrogel wound dressing with NO/O2 dual gas-releasing property promotes infected diabetic wound healing

It is still challenging to design stimuli-responsive smart hydrogel dressing to promote bacteria-infected diabetic wound healing from the whole healing stage by intelligently responding to external stimuli or wound microenvironment. In addition, nitric oxide (NO) and oxygen (O 2 ) have been shown to accelerate diabetic wound healing by promoting angiogenesis and alleviating hypoxia. A series of NIR/glucose stimuli-responsive multifunctional smart hydrogels with NO/O 2 dual gas-releasing properties was designed based on N-carboxyethyl chitosan-grafted-phenylboronic acid (CECP), oxidized dextran (OD), ε-polylysine (EPL)-coated manganese dioxide (EMn), and β-cyclodextrin-reduced graphene oxide/N, N’-di-sec-butyl-N, N’-dinitroso-1,4-phenylenediamine (rGB) via dual dynamic crosslinking to promote bacteria-infected diabetic wound healing. The added rGB and EMn as photothermal agents rapidly kill bacteria through photothermal therapy. Meanwhile, rGB endows CECP/OD/EMn/rGB hydrogels to release NO under NIR stimulation to promote angiogenesis. Nanozyme EMn with catalase (CAT)/superoxide dismutase (SOD)-like activity can scavenge ROS and release O 2 to alleviate hypoxia and oxidative stress. The phenylboronic acid in CECP forming phenylboronate ester structure endows hydrogel with glucose-controlled release of doxycycline. NIR/glucose stimuli-responsive CECP/OD/EMn/rGB hydrogels with NO/O 2 dual gas-releasing property in a full-thickness skin wound-infected diabetic model reduced the inflammation, promoted wound contraction, collagen deposition, angiogenesis, and alleviated wound hypoxia, providing new ideas for treating bacteria-infected diabetic wounds.