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基于铈/锌复合材料的多功能透明质酸微针贴片促进糖尿病创面愈合

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

机构信息

Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, P. R. China.

School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, 230032, P. R. China.

出版信息

Adv Healthc Mater. 2023 Sep;12(24):e2300725. doi: 10.1002/adhm.202300725. Epub 2023 May 3.

DOI:10.1002/adhm.202300725
PMID:37086396
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 and Ce / . Additionally, ZCO-HA exhibits 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 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-κB signaling pathway.

摘要

慢性非愈合性糖尿病伤口由于高血糖、血管生成受阻、生物膜感染和过度氧化应激导致伤口愈合困难,情况日益严重,死亡率和致残率较高。本文报道了一种多组分酶响应天然聚合物,即透明质酸(HA)微针,嵌入铈/锌基纳米材料(ZCO)中,用于治疗糖尿病伤口。ZCO-HA 可以通过可调释放 Zn 和 Ce/破坏细菌的氧化平衡,杀死细菌,并清除活性氧(ROS),从而减轻氧化应激。此外,ZCO-HA 通过核因子 kappa-B(NF-κB)通路表现出良好的抗炎活性,降低巨噬细胞的炎症状态,促进细胞增殖、迁移和血管生成。体外实验表明,ZCO-HA 伴随小鼠成纤维细胞迁移,促进人脐静脉内皮细胞管形成。STZ 诱导的糖尿病小鼠体内研究表明,这种微针加速了伤口愈合,且无全身毒性。RNA 转录组测序表明,多组分 HA 微针通过细胞迁移加速糖尿病伤口愈合,并通过 NF-κB 信号通路抑制小鼠的炎症反应和氧化损伤。

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