Hyaluronic Acid Applications in Periodontal Therapy

Hyaluronic acid (HA) is a naturally occurring polysaccharide prevalent in the extracellular matrix of connective tissues. Its viscoelastic, hydrophilic and bioactive properties have been harnessed in periodontal therapy to support wound healing, modulate inflammation and combat pathogenic biofilms. In non-surgical approaches, topical or subgingival application of HA adjuncts to scaling and root-planing has been shown to enhance reductions in probing depth and bleeding on probing, while promoting gains in clinical attachment. In surgical and regenerative procedures, HA can serve as a carrier for osteoconductive graft materials, a scaffold for cellular infiltration or a vehicle for oxygen delivery in hypoxic periodontal defects. Mechanistically, HA interacts with cell-surface receptors to regulate fibroblast proliferation, cytokine expression and angiogenesis, as well as exerting bacteriostatic effects against key periodontal pathogens. Recent innovations include cross-linked formulations that prolong residence time in the pocket, combination gels with botanical extracts to boost soft tissue repair and oxygen-releasing dispersions that aim to overcome local hypoxia and enhance tissue regeneration. Across diverse clinical and laboratory settings, HA stands out for its biocompatibility, versatility and contribution to minimally invasive periodontal care with potential to improve long-term oral health outcomes.

Research from Nature Portfolio

A recent split-mouth clinical trial investigated a combined green tea and hyaluronic acid gel applied to post-extraction sockets following third molar removal. In vitro exposure of human fibroblasts to the gel upregulated genes involved in cell survival, proliferation and angiogenesis, including AKT, CDKs and VEGF. Clinically, sites treated with the gel exhibited reduced swelling and exudate, fewer secondary interventions and significantly greater alveolar bone density at 90 days compared with placebo. These findings demonstrate a synergistic effect of HA and bioactive plant polyphenols in enhancing soft tissue healing and early bone regeneration, suggesting a promising adjunct for improving postoperative recovery in oral surgery.

Hyaluronic Acid Applications in Periodontal Therapy publication trend

The graph below shows the total number of articles in hyaluronic acid applications in periodontal therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Hyaluronic acid: Endogenous glycosaminoglycan that hydrates tissues, modulates inflammation and supports cellular migration.

Periodontitis: Chronic inflammatory disease characterised by destruction of the periodontium and formation of periodontal pockets.

Non-surgical periodontal therapy: Mechanical removal of subgingival biofilm and calculus by scaling and root-planing without surgical incision.

Probing pocket depth: Distance from the gingival margin to the base of the periodontal pocket, measured in millimetres.

Clinical attachment level: Position of the periodontal soft tissue relative to a fixed tooth landmark, indicating tissue support.

Biofilm: Structured microbial community attached to a surface within a self-produced extracellular matrix.

Cytokine: Small secreted protein that mediates and regulates immune and inflammatory responses.

Angiogenesis: Formation of new blood vessels essential for tissue repair and regeneration.

References

1. Adjunctive use of hyaluronic acid in non-surgical periodontal therapy: A systematic review and meta-analysis. Journal of Dentistry (2025).
2. The Effect of Adjunctive Use of Hyaluronic Acid on Prevalence of Porphyromonas gingivalis in Subgingival Biofilm in Patients with Chronic Periodontitis: A Systematic Review. Pharmaceutics (2023).
3. The Effect of Hyaluronic Acid Gel on Periodontal Parameters, Pro-Inflammatory Cytokines and Biochemical Markers in Periodontitis Patients. Gels (2023).
4. Oxygen-Releasing Hyaluronic Acid-Based Dispersion with Controlled Oxygen Delivery for Enhanced Periodontal Tissue Engineering. International Journal of Molecular Sciences (2023).
5. In-vitro effects of different hyaluronic acids on periodontal biofilm-immune cell interaction. Frontiers in Cellular and Infection Microbiology (2024).
6. Green tea and hyaluronic acid gel enhance fibroblast activation and improves the gingival healing post-third molar extraction. Scientific Reports (2024).
7. Periodontal Wound Healing and Tissue Regeneration: A Narrative Review. Pharmaceuticals (2021).