Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/ijms20153722
Keywords
hyaluronan; N-butyrylation; anti-inflammation; angiogenesis; lymphangiogenesis
Funding
- National Natural Science Foundation of China [31700713]
- Outstanding Youth Foundation from the Department of Science and Technology of Jilin Province, China [20170520046JH, 20170520034JH]
- Department of Education of Jilin Province, China [JJKH20190099KJ, JJKH20180174KJ]
- Jilin Province Development and Reform Commission, China [2019C049-9]
- Fundamental Research Funds for the Central Universities, China
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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.
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