Biomaterials releasing drug responsively to promote wound healing via regulation of pathological microenvironment

Wound healing is characterized by complex, orchestrated, spatiotemporal dynamic processes. Recent findings demonstrated suitable local microenvironments were necessities for wound healing. Wound microenvironments include various biological, biochemical and physical factors, which are produced and regulated by endogenous biomediators, exogenous drugs, and external environment. Successful drug delivery to wound is complicated, and need to overcome the destroyed blood supply, persistent inflammation and enzymes, spatiotemporal requirements of special supplements, and easy deactivation of drugs. Triggered by various factors from wound microenvironment itself or external elements, stimuli-responsive biomaterials have tremendous advantages of precise drug delivery and release. Here, we discuss recent advances of stimuli-responsive biomaterials to regulate local microenvironments during wound healing, emphasizing on the design and application of different biomaterials which respond to wound biological/biochemical microenvironments (ROS, pH, enzymes, glucose and glutathione), physical microenvironments (mechanical force, temperature, light, ultrasound, magnetic and electric field), and the combination modes. Moreover, several novel promising drug carriers (microbiota, metal-organic frameworks and microneedles) are also discussed.