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

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.