Multifunctional Hyaluronic Acid Microneedle Patch Embedded by Cerium/Zinc‐Based Composites for Accelerating Diabetes Wound Healing

Abstract 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. 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 is reported. 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 exhibits good anti‐inflammatory activity through the nuclear factor kappa‐B (NF‐ κ B) 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 reveal that this microneedle accelerates wound healing without systemic toxicity. RNA transcriptome sequencing illustrates that the multicomponent HA microneedle accelerates wound healing in diabetes through cell migration and inhibits inflammatory reactions and oxidative damage in mice via the NF‐ κ B signaling pathway.