Hybrid Hydrogels for Immunoregulation and Proangiogenesis through Mild Heat Stimulation to Accelerate Whole-Process Diabetic Wound Healing.

Abstract

Intense and persistent oxidative stress, excessive inflammation, and impaired angiogenesis severely hinder diabetic wound healing. Bioactive hydrogel dressings with immunoregulatory and proangiogenic properties have great promise in treating diabetic wounds. However, the therapeutic effects of dressings always depend on drugs with side effects, expensive cytokines, and cell therapies. Herein, a novel dynamic borate-bonds crosslinked hybrid multifunctional hydrogel dressings with photothermal properties are developed to regulate the microenvironment of diabetic wound sites and accelerate the whole process of its healing without additional medication. The hydrogel is composed of phenylboronic acid-modified chitosan and hyaluronic acid (HA) crosslinked by tannic acid (TA) through borate bonds and Prussian blue nanoparticles (PBNPs) with photothermal response characteristics are embedded in the polymer networks. The results indicate hydrogels show inherent broad-spectrum antioxidative activities through the integrated interaction of borate bonds, TA, and PBNPs. Meanwhile, combined with the regulation of macrophage phenotype by HA, the inflammatory microenvironment of diabetic wounds is transformed. Moreover, the angiogenesis is then enhanced by the mild photothermal effect of PBNPs, followed by promoted epithelialization and collagen deposition. In summary, this hybrid hydrogel system accelerates all stages of wound repair through antioxidative stress, immunomodulation, and proangiogenesis, showing great potential applications in diabetic wound management.