Visualization of the Relationship Between Hyaluronic Acid and Wound Healing: A Bibliometric Analysis

Wound healing is a complex process with significant economic implications. Hyaluronic acid (HA), valued for its adaptability and biocompatibility, shows the potential to improve multiple facets of wound healing. Despite the expanding literature on the use of HA in wound care, a comprehensive analysis of its scholarly evolution is lacking. This study employs a bibliometric approach to objectively evaluate trends in scholarly publications regarding HA's role in promoting wound healing.

We searched in the Web of Science Core Collection (WoSCC) for articles published from January 1, 2000 to March 31, 2024. We extracted relevant information about using HA to promote wound healing following a thorough screening process. Subsequently, a comprehensive analysis was undertaken on a total of 1886 publications. The analysis utilized GraphPad Prism 9, CiteSpace6.1.6, VOSviewer1.6.19, the Online Analysis Platform of Literature Metrology (http://bibliometric.com/), GeneMANIA (https://genemania.org/), and Metascape (https://metascape.org/gp/index.html#/main/step1).

We retrieved 2424 publications on hyaluronic acid (HA) and wound healing from the Web of Science Core Collection, covering the period from January 2000 to March 2024, and selected 1886 for analysis. The results show a significant increase in publications since 2016, reflecting a growing focus on this field. Currently, China's publication volume has surpassed the United States since 2017, indicating a significant rise in China's influence in this area. Using CiteSpace software for co-citation analysis, we identified eight main research clusters, including promoted wound healing, injured tissue, and advanced multi-targeted composite biomaterial. Key research areas involve the role and mechanisms of hyaluronic acid in tissue repair, particularly its applications in growth factor production and regenerative therapy. Analyzing keyword co-occurrence and burst data with VOSviewer, we identified research hotspots focused on biomaterials, such as nanoparticles and hydrogels, and their antibacterial properties. The keyword "CD44" showed a long burst period, while "antibacterial" had the highest burst intensity in 2022. We identified the top 21 genes extensively studied in hyaluronic acid and wound healing, including CD44, VEGF, and TGF-β. These genes are mainly involved in regulating cell migration, adhesion, proliferation, and cytokine activity. GO enrichment and KEGG pathway analyses indicate that these genes are associated with key signaling pathways, such as MAPK and EGFR, revealing the primary mechanisms hyaluronic acid promotes wound healing.

This pioneering study provides the first comprehensive bibliometric analysis of HA in wound healing. Covering the period from January 1, 2000 to March 31, 2024, it reveals a significant expansion in annual scholarly production. Current research emphasizes the development of HA-based biomaterials for enhancing wound healing.