Impact of Hyaluronic Acid and Other Re-Epithelializing Agents in Periodontal Regeneration: A Molecular Perspective

Abstract

This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms.

Keywords: connective cells; gingival tissues; hyaluronic acid; periodontal regeneration; periodontitis.

Figure 1

Structure of disaccharide repeating unit of HA. The unit of HA is composed of β-(1,4)-glucuronic acid and β-(1,3)-N-acetylglucosamine linked together by β-1,3 and β-1,4 glycosidic bonds. The molecular weight of this molecule depends on the number of repetitions of the disaccharide unit (n).

Figure 2

Wound healing process. It comprises hemostasis, inflammation, proliferation, and remodeling. Reprinted with permission from [20]. Copyright 2024 American Chemical Society.

Figure 3

Schematic representation of periodontal tissue engineering.

Figure 4

The synthesis and effects of PGE2 in periodontitis. From [72], under Creative Commons Attribution 4.0 International License.