A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen
A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen
复制标题
低分子量透明质酸衍生物通过调节促炎症、促进上皮化和新血管形成以及重塑胶原蛋白来加速切除伤口愈合
DOI：
10.3390/ijms20153722
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Anastassiades, Tassos P.
中科院分区：
文献类型：
--
作者：
Gao, Yin;Sun, Yao;Anastassiades, Tassos P.
皮肤伤口愈合的细胞和分子机制的最新知识促进了医疗产品的发展。然而，由于愈合过程的复杂性，患者仍然遭受当前治疗的失败，因此迫切需要新的治疗方法。以前，我们的实验室生产了一系列低分子量透明质酸（LMW-HA）片段，其中一部分葡萄糖胺部分被化学N-酰基取代。具体而言，N-丁酰化导致巨噬细胞系统中的抗炎特性，并且我们证明了N-酰基取代基在调节LMW-HA的炎症反应中的重要性。我们已经建立了一个机构间的合作计划，以检查N-丁酰化的LMW-HA（BHA）的生物医学应用。在本研究中，在体外和体内评估了BHA用于皮肤愈合的潜力。因此，BHA相对于商业伤口护理产品显著促进皮肤愈合。相比之下，母体部分脱乙酰化的LMW-HA（DHA）和再乙酰化的DHA（AHA）显著延迟伤口闭合，证明了LMW-HA的这种N-酰化在伤口愈合中的特异性。机制研究揭示了BHA介导的治疗效果是通过靶向伤口愈合的三个阶段（即，炎症、增殖和成熟），证明了BHA在皮肤伤口愈合中临床转化的显著潜力。
Recent knowledge of the cellular and molecular mechanisms underlying cutaneous wound healing has advanced the development of medical products. However, patients still suffer from the failure of current treatments, due to the complexity of healing process and thus novel therapeutic approaches are urgently needed. Previously, our laboratories produced a range of low molecular weight hyaluronic acid (LMW-HA) fragments, where a proportion of the glucosamine moieties were chemically N-acyl substituted. Specifically, N-butyrylation results in anti-inflammatory properties in a macrophage system, and we demonstrate the importance of N-acyl substituents in modulating the inflammatory response of LMW-HA. We have set up an inter-institutional collaborative program to examine the biomedical applications of the N-butyrylated LMW-HA (BHA). In this study, the potentials of BHA for dermal healing are assessed in vitro and in vivo. Consequently, BHA significantly promotes dermal healing relative to a commercial wound care product. By contrast, the parent partially de-acetylated LMW-HA (DHA) and the re-acetylated DHA (AHA) significantly delays wound closure, demonstrating the specificity of this N-acylation of LMW-HA in wound healing. Mechanistic studies reveal that the BHA-mediated therapeutic effect is achieved by targeting three phases of wound healing (i.e., inflammation, proliferation and maturation), demonstrating the significant potential of BHA for clinical translation in cutaneous wound healing.