Bacterial responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing

Abstract There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacterial responsive self-activating antibacterial property and multiple nanozyme activities to remodel regeneration microenvironment to significantly promote infected wound healing. Specifically, pH-responsive H2O2 self-supplying composite nanozyme (MSCO) and pH/enzyme-sensitive bacterial-responsive triblock micelles encapsulated with lactate oxidase (PPEL) were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan (CA) and phenylboronic acid-modified oxidized dextran (ODP) to form a cascade bacterial-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide (NO) release. The composite hydrogel showed ‘self-diagnostic’ treatment for changes in the wound microenvironment. Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new way for the design of intelligent wound dressings.