Microenvironment-feedback regulated hydrogels as living wound healing materials

Physiological microenvironments present a time-dependent variation during pathogenic or therapeutic processes, which call for life-like biomaterials of dynamic adaptation. However, current prevailed biomaterials maintain a passively responsive mode and lack autonomous and interactive dynamics. Striving for a paradigm of microenvironment interactive and self-regulatory medical agents as next-generation of biomaterials is of desperate need. Herein, we develop a microenvironment-feedback hydrogel as a living dressing biomaterial catering diabetic chronic wounds. This dynamic hydrogel leverages the initial alkaline pH of the wound bed as fuel and employs biocatalytic acid generation as the anti-fuel. By coupling this feedback loop to pH-regulated imine crosslinks, the hydrogel facilitates adaptive sol-gel cycling with programmable glucose oxidase (GOx) release in a Type-I diabetic mouse model. Thus, homeostatic wound pH and blood glucose levels are achieved, favoring accelerated in vivo wound healing and tissue repair. Chronic wounds typically exhibit dynamic variations within the complex wound microenvironment over time. Here, Cheng et al. develop a microenvironment-feedback hydrogel to achieve homeostatic wound pH and blood glucose levels to accelerate repair of diabetic chronic wounds.