The Emerging Role of Hyaluronic Acid as a Multifunctional Regenerative Agent in Periodontal Healing

Periodontitis is a multifactorial inflammatory disease characterized by dysbiotic microbial communities and progressive destruction of the supporting periodontal tissues, ultimately leading to alveolar bone loss. Achieving predictable periodontal regeneration remains a major clinical challenge because of the complex interplay between inflammation, microbial burden, and tissue remodeling. In this context, hyaluronic acid (HA), a naturally occurring component of the extracellular matrix (ECM), has gained increasing attention as a bioactive adjunct in periodontal therapy. This narrative review aims to describe current evidence regarding the biological properties, molecular mechanisms, and clinical applications of HA in periodontal therapy, with a particular focus on its immunomodulatory, antimicrobial, and regenerative potential. Available data indicate that HA exerts molecular weight-dependent effects, ranging from anti-inflammatory and extracellular matrix-stabilizing actions to osteogenic and immunostimulatory responses. Clinically, HA has been investigated as an adjunct in both nonsurgical and surgical periodontal therapies, as well as in minimally invasive regenerative approaches, as it has favorable effects on inflammation control, soft tissue healing, and clinical attachment gain. Recent advances in materials science have further expanded the role of HA through the development of engineered hydrogels and hybrid delivery systems incorporating nanoparticles, bioactive glass, growth factors, or antimicrobial agents, which have demonstrated promising osteogenic and antibacterial outcomes in preclinical models. However, the interpretation of existing evidence is limited by heterogeneity in HA formulations, short follow-up periods, and inconsistent reporting of periodontal defect morphology. Future research should focus on standardized, well-designed preclinical and clinical studies integrating histological, radiographic, immunological, and microbiological assessments to distinguish true periodontal regeneration from repair and to optimize HA-based strategies tailored to specific defect configurations.