Inflammation‐Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis

An inflammation-responsive hydrogel incorporating Prussian blue nanoparticles is designed to reprogram the immune microenvironment for preserved bioavailability of loaded vascular endothelial growth factor, therefore augmenting the angiogenic efficacy to promote the healing process of diabetic wounds.

Abstract

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.