Silk Sericin-based ROS-Responsive Oxygen Generating Microneedle Platform Promotes Angiogenesis and Decreases Inflammation for Scarless Diabetic Wound Healing

Abstract

Diabetic foot ulcer typically undergoes a delayed wound-healing process owing to the disordered microenvironment, including persistent inflammation, long-term hypoxia, and excessive fibrosis, eventually leading to severe disabilities and other poor outcomes. However, current strategies cannot meet the dynamic demands during the wound-healing process. Herein, a reactive oxygen species (ROS)–responsive oxygen-generating microneedle platform, consisting of a sericin-based glucose-responsive hydrogel loaded with verteporfin, for effective diabetic wound healing is proposed. Under a highly oxidative microenvironment, the functionalized sericin protein depletes overproduced ROS to generate oxygen, which can not only alleviate the hypoxic microenvironment and promote angiogenesis by activating extracellular signal-regulated kinase and Heme Oxygenase-1 pathways but also decrease the expression of proinflammatory cytokines. Moreover, the hyperglycaemic condition triggers the gradual dissociation of this microneedle platform and promotes the release of verteporfin to enhance scarless re-epithelization via inhibiting the yes-associated protein signal. This versatile sericin microneedle system integrates advantageous features including inflammation alleviation, angiogenesis promotion, and scar inhibition capabilities, accelerates diabetic wound repair in vivo, and offers a novel approach for oxygen self-supply and wound microenvironment remodeling.