Multifunctional Hyaluronic Acid Microneedle Patch Embedded by Cerium/Zinc-based Composites for Accelerating Diabetes Wound Healing.

Chronic nonhealing diabetic wounds are becoming increasingly severe, with high rates of mortality and disability, owing to the difficulty in wound healing caused by hyperglycemia, blocked angiogenesis, biofilm infection, and excessive oxidative stress. W e report a multicomponent enzyme-responsive natural polymer, a hyaluronic acid (HA) microneedle, embedded in a cerium/zinc-based nanomaterial (ZCO) for the treatment of diabetic wounds. ZCO-HA can destroy the oxidation balance of bacteria, kill bacteria, and scavenge reactive oxygen species (ROS) to alleviate oxidative stress via the adjustable release of Zn 2+ and Ce 3+ / 4+ . Additionally, ZCO-HA exhibited good anti-inflammatory activity through the nuclear factor kappa-B (NF-κB) pathway, which reduces the inflammatory state of macrophages and promotes cell proliferation, migration, and angiogenesis. In vitro experiments shows that ZCO-HA accompanies mouse fibroblast migration, promoting human umbilical vein endothelial cell tube formation. In vivo studies in mice with streptozotocin-induced (STZ)-induced diabetes revealed that this microneedle accelerated wound healing without systemic toxicity. RNA transcriptome sequencing illustrated that the multicomponent HA microneedle accelerated wound healing in diabetes through cell migration and inhibited inflammatory reactions and oxidative damage in mice via the NF-κB signaling pathway. This article is protected by copyright. All rights reserved.