Hyaluronic Acid-based ROS-responsive Multifunctional Injectable Hydrogel Platform Accelerating Diabetic Wound Healing.

Diabetic wounds are more likely to develop into complex and severe chronic wounds. The objective of this study is to develop and assess a reactive oxygen species (ROS)-responsive multifunctional injectable hydrogel for the purpose of diabetic wound healing. We successfully synthesized a multifunctional hydrogel (HA@Cur@Ag) with dual antioxidant, antibacterial, and anti-inflammatory properties by crosslinking thiol hyaluronic acid (SH-HA) and disulfide-bonded hyperbranched polyethylene glycol (HB-PBHE) through Michael addition while incorporating curcumin liposomes and silver nanoparticles (AgNPs). The HA@Cur@Ag hydrogel exhibited favourable biocompatibility, degradability and injectivity. The outcomes of in vitro and in vivo experiments demonstrated that the hydrogel could effectively be loaded with and release curcumin liposomes, as well as silver ions, thereby facilitating diabetic wound healing through multiple mechanisms, including ROS scavenging, bactericidal activity, anti-inflammatory effects, and the promotion of angiogenesis. Transcriptome sequencing revealed that the HA@Cur@Ag hydrogel effectively suppressed the activation of the tumour necrosis factor (TNF)/ nuclear factor κB (NF-κB) pathway to ameliorate oxidative stress and inflammation in diabetic wounds. These findings suggested that this ROS-responsive multifunctional injectable hydrogel, which possessed the ability to precisely coordinate and integrate intricate biological and molecular processes involved in wound healing, exhibited notable potential for expediting diabetic wound healing. This article is protected by copyright. All rights reserved.