Asymmetric double layer Janus hydrogels with programmed nitric oxide release for chronic diabetic wound healing

Chronic diabetic wounds pose a significant challenge in wound care due to delayed healing and high infection rates. Nitric oxide (NO) has been shown to promote wound healing through its anti-inflammatory, angiogenic, and antimicrobial properties. However, the non-uniform and uncontrollable release of NO limits their therapeutic efficacy, especially the pro-inflammatory effects induced by high local concentrations of NO hindered its application in diabetic chronic wounds. To balance antibacterial efficacy with anti-inflammatory effects, we developed an asymmetric double-layer hydrogel system for programmed NO release. High concentration NO was released from outer layer through photothermal action, which can rapidly clear bacteria and biofilms. The inner layer encapsulated with glucose oxidase (GOX) and L-arginine, performs multiple functions. GOX consumes glucose to generate hydrogen peroxide, which can oxidize L-arginine to form NO. This low and sustained NO released from inner layer exert anti-inflammatory effects. Simultaneously, the low-glucose environment can further inhibit the growth of bacteria and promote wound healing. The results showed that Janus hydrogels promoted vascular regeneration and significantly facilitated the repair of chronic diabetic wounds via modulating the EGFR/AKT signaling pathway. This Janus double-layer hydrogel design is tailored to the specific needs of diabetic wounds, offering precise control over NO release.