Clinical efficacy of hyaluronic acid in the regenerative treatment of periodontal intrabony defects: integrative review

Authors

  • Vittoria Delmastro Student of Dental Medicine, Faculty of Health Sciences, Universidade Fernando Pessoa, Porto, Portugal https://orcid.org/0009-0008-7843-1819
  • Filipe Augusto Martins Professor of Periodontology of Faculty of Health Sciences, University Fernando Pessoa (UFP), Porto, Portugal https://orcid.org/0000-0002-8460-6178
  • Tiago José Martins Professor of Periodontology of Faculty of Health Sciences, University Fernando Pessoa (UFP), Porto, Portugal

DOI:

https://doi.org/10.62741/ahrj.v3iSuppl.%202.223

Keywords:

hyaluronic acid, periodontal regeneration, intrabony defects, periodontal intrabony defect

Abstract

Introduction: The regeneration of periodontal intrabony defects represents a relevant clinical challenge due to their anatomical complexity and the unpredictability of regenerative outcomes. Hyaluronic acid, a key component of the extracellular matrix, has been proposed as an adjunctive agent in periodontal regenerative therapies.

Objectives: To critically analyze the available scientific evidence on the clinical and radiographic efficacy of hyaluronic acid in the regenerative treatment of periodontal intrabony defects.

Methodology: An integrative literature review was conducted using the PubMed, Web of Science, Cochrane Library, and B-On databases, including studies published between 2018 and 2025. The search strategy combined MeSH terms and the keywords related to hyaluronic acid and periodontal regeneration following PRISMA guidelines; 11 studies were included.

Results: The use of hyaluronic acid, particularly as an adjunctive agent, is associated with significant improvements in clinical periodontal parameters, clinical attachment level gain and probing pocket depth reduction, as well as radiographic evidence of bone fill in specific contexts. When combined with open flap debridement, hyaluronic acid demonstrated additional clinical benefits, particularly in the short term. In minimally invasive approaches and when compared with enamel matrix derivatives, a positive effect was mainly observed during the early healing phases, without sustained differences in the medium term.

Discussion: Current evidence suggests that hyaluronic acid improves periodontal regenerative outcomes, particularly during early healing, but its long-term benefits remain uncertain. While hyaluronic acid appears to be a promising adjunctive therapy and a potential alternative to enamel matrix derivatives, further high-quality studies are needed to confirm its clinical effectiveness.

Conclusion: Hyaluronic acid appears to be a promising adjunctive therapeutic option in the regenerative treatment of periodontal intrabony defects, contributing to improvements in clinical parameters and to the optimization of early healing.

References

Iorio‑Siciliano V, et al. Non‑surgical treatment of moderate periodontal intrabony defects with adjunctive cross‑linked hyaluronic acid: a single‑blinded randomized controlled clinical trial. J Clin Periodontol. 2025;52(3):310‑322. doi:10.1111/jcpe.14078.

Ezer UG, Gunpinar S. Local application of 0.8% hyaluronic acid gel as an adjunct to minimally invasive nonsurgical treatment of periodontal intrabony defects: a randomized clinical trial. J Periodontal Res. 2025;60(2):215‑225. doi:10.1111/jre.13331.

Rodríguez M, et al. Comparison of cross‑linked hyaluronic acid vs enamel matrix derivative for periodontal regeneration: an 18‑month randomized clinical trial. Clin Oral Investig. 2025;29(3):1917‑1925. doi:10.1007/s00784‑025‑06278‑5.

Ostos‑Aguilar BI, et al. Clinical efficacy of hyaluronic acid in the treatment of periodontal intrabony defects: a systematic review and meta‑analysis. Clin Oral Investig. 2023;27(5):1923‑1935. doi:10.1007/s00784‑022‑04855‑6.

Mamajiwala AS, et al. Clinical and radiographic evaluation of 0.8% hyaluronic acid as an adjunct to open flap debridement in the treatment of periodontal intrabony defects: randomized controlled clinical trial. Clin Oral Investig. 2021;25(9):5257‑5271. doi:10.1007/s00784‑021‑03834‑7.

Pilloni A, et al. Healing of intrabony defects following regenerative surgery by means of single‑flap approach in conjunction with either hyaluronic acid or an enamel matrix derivative: a 24‑month randomized clinical trial. Clin Oral Investig. 2021;25(8):5095‑5107. doi:10.1007/s00784‑021‑03822‑x.

Vela OC, et al. Clinical and radiographic evaluation of intrabony periodontal defects treated with hyaluronic acid or enamel matrix proteins: a 6‑month prospective study. Oral Health Prev Dent. 2024;22(1):257‑270. doi:10.3290/j.ohpd.b5569745.

Božić D, et al. Treatment of intrabony defects with a combination of hyaluronic acid and deproteinized porcine bone mineral. Materials (Basel). 2021;14(22):6795. doi:10.3390/ma14226795.

Bădărău‑Suster AM, et al. Recent advances in regenerative therapies in periodontology. Dent J (Basel). 2025;13(12):564. doi:10.3390/dj13120564.

Rodríguez‑Aranda M, et al. Hyaluronic acid for periodontal tissue regeneration in intrabony defects: a systematic review. Dent Rev. 2022;2(2):100057. doi:10.1016/j.dentre.2022.100057.

Kaur J, et al. Comparative evaluation of bioresorbable membrane with and without hyaluronic acid in the treatment of intra‑bony defects: a clinical and radiographic study. J Pharm Bioallied Sci. 2025;17(Suppl 2):S2894‑S2896. doi:10.4103/jpbs.jpbs_1038_25.

Cortellini P, Tonetti MS. Clinical concepts for regenerative therapy in intrabony defects. Periodontol 2000. 2015;68(1):282‑307. doi:10.1111/prd.12048.

Nibali L, et al. Regenerative surgery versus access flap for the treatment of intra‑bony periodontal defects: a systematic review and meta‑analysis. J Clin Periodontol. 2020;47(Suppl 22):320‑351. doi:10.1111/jcpe.13237.

Sculean A, et al. Regeneration of periodontal tissues: combinations of barrier membranes and grafting materials—biological foundation and preclinical evidence. J Clin Periodontol. 2008;35(suppl 8):106‑116. doi:10.1111/j.1600‑051X.2008.01263.x.

Trombelli L, et al. A systematic review of graft materials and biological agents for periodontal intraosseous defects. J Clin Periodontol. 2002;29(suppl 3):117‑135. doi:10.1034/j.1600‑051X.29.s3.7.x.

Stavropoulos A, et al. Medium‑ and long‑term clinical benefits of periodontal regenerative/reconstructive procedures in intrabony defects: systematic review and network meta‑analysis of randomized controlled clinical studies. J Clin Periodontol. 2021;48(Suppl 22):410‑430. doi:10.1111/jcpe.13409.

Nibali L, et al. Periodontal infrabony defects: systematic review of healing by defect morphology following regenerative surgery. J Clin Periodontol. 2021;48(Suppl 22):100‑113. doi:10.1111/jcpe.13381.

Reynolds MA, et al. Periodontal regeneration—Infrabony defects: a consensus report from the AAP Regeneration Workshop. J Periodontol. 2015;86(2 Suppl):S105‑S107. doi:10.1902/jop.2015.140378.

Cortellini P, Tonetti MS. Minimally invasive surgical technique and enamel matrix derivative in intrabony defects. J Clin Periodontol. 2007;34(1):87‑93. doi:10.1111/j.1600‑051X.2007.01144.x.

Casale M, et al. Hyaluronic acid: perspectives in dentistry. A systematic review. Int J Immunopathol Pharmacol. 2016;29(4):572‑582. doi:10.1177/0394632016652906.

Eliezer M, et al. Hyaluronic acid as adjunctive to non‑surgical and surgical periodontal therapy: a systematic review and meta‑analysis. Clin Oral Investig. 2019;23(9):3423‑3435. doi:10.1007/s00784‑019‑03012‑w.

Dahiya P, Kamal R. Hyaluronic acid: a boon in periodontal therapy. N Am J Med Sci. 2013;5(5):309‑315. doi:10.4103/1947‑2714.112473.

Trombelli L, et al. The adjunctive effect of a cross‑linked hyaluronic acid gel in non‑surgical periodontal therapy: a randomized clinical trial. J Periodontol. 2019;90(12):1253‑1262. doi:10.1002/JPER.19‑0028.

Nibali L, et al. Minimally invasive non‑surgical approach for the treatment of periodontal intrabony defects: a retrospective analysis. J Clin Periodontol. 2015;42(9):853‑859. doi:10.1111/jcpe.12443.

Ribeiro FV, et al. Clinical and patient‑centered outcomes after minimally invasive non‑surgical or surgical approaches for the treatment of intrabony defects: a randomized clinical trial. J Periodontol. 2011;82(9):1256‑1266. doi:10.1902/jop.2011.100680.

Windisch P, et al. The role of surgical flap design (minimally invasive flap vs. extended flap with papilla preservation) on the healing of intrabony defects treated with an enamel matrix derivative: a 12‑month randomized controlled clinical trial. Clin Oral Investig. 2022;26(2):1811‑1821. doi:10.1007/s00784‑021‑04172‑4.

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Published

07-08-2026