Clinical Oral Investigations

, Volume 23, Issue 9, pp 3423–3435 | Cite as

Hyaluronic acid as adjunctive to non-surgical and surgical periodontal therapy: a systematic review and meta-analysis

  • Meizi Eliezer
  • Jean-Claude Imber
  • Anton SculeanEmail author
  • Nikolas Pandis
  • Sorin Teich



To evaluate the potential added benefit of the topical application of hyaluronic acid (HA) on the clinical outcomes following non-surgical or surgical periodontal therapy.

Materials and methods

A systematic search was performed in Medline, Embase, Cochrane, Web of Science, Scopus and Grey literature databases. The literature search was preformed according to PRISMA guidelines. The Cochrane risk of bias tool was used in order to assess the methodology of the included trials. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) between the treatment and controls were estimated using the random-effect model for amount of bleeding on probing (BOP), probing depth (PD) reduction and clinical attachment level (CAL) gain. In order to minimize the bias and to perform meta-analysis, only randomized clinical studies (RCTs) were selected.


Thirteen RCTs were included: 11 on non-surgical periodontal treatment and two on surgical periodontal treatment. Overall analysis of PD reduction, CAL gain and BOP reduction in non-surgical therapy with adjunctive HA presented WMD of − 0.36 mm (95% CI − 0.54 to − 0.19 mm; p < 0.0001), 0.73 mm (95% CI 0.28 to 1.17 mm; p < 0.0001) and − 15% (95% CI − 22 to − 8%; p < 0.001) respectively, favouring the application of HA. The overall analysis on PD and CAL gain in surgical therapy with adjunctive HA presented WMD of − 0.89 mm (95% CI − 1.42 to − 0.36 mm; p < 0.0001) for PD reduction and 0.85 mm (95% CI 0.08 to 1.62 mm; p < 0.0001) for CAL gain after 6–24 months favouring the treatment with HA. However, comparison presented considerable heterogeneity between the non-surgical studies and a high risk of bias in general.


Within their limits, the present data indicate that the topical application of HA may lead to additional clinical benefits when used as an adjunctive to non-surgical and surgical periodontal therapy. However, due to the high risk of bias and heterogeneity, there is a need for further well-designed RCTs to evaluate this material in various clinical scenarios.

Clinical relevance

The adjunctive use of HA may improve the clinical outcomes when used in conjunction with non-surgical and surgical periodontal therapy.


Hyaluronic acid Hyaluronan Periodontitis Surgical periodontal therapy Non-surgical periodontal therapy 



The work was supported by the authors’ own institutions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study (e.g. systematic review and meta-analysis), formal consent is not required.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Meizi Eliezer
    • 1
  • Jean-Claude Imber
    • 1
    • 2
  • Anton Sculean
    • 1
    Email author
  • Nikolas Pandis
    • 3
  • Sorin Teich
    • 4
  1. 1.Department of PeriodontologyUniversity of BernBernSwitzerland
  2. 2.Department of Periodontology and Operative DentistryUniversity of MainzMainzGermany
  3. 3.Department of Orthodontics and Dentofacial OrthopedicsUniversity of BernBernSwitzerland
  4. 4.Medical University of South CarolinaJames B. Edwards College of Dental MedicineCharlestonUSA

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