Aim: The main purpose of the present study was to investigate the potential benefit of local use of hyaluronic acid as an adjunct to periodontal therapy, since commercial products of hyaluronic acid (HA), due to its anti-inflammatory and anti-bacterial actions and its significant role in wound repair, have been proposed as adjuncts to either nonsurgical or surgical periodontal therapy. Materials and methods: A total of 19 electronic databases were searched and the appropriate studies were identified with the use of specific eligibility criteria, according to PRISMA guidelines. Two reviewers independently screened and selected the studies and made the data extraction and the assessment of risk of bias, by using the Cochrane risk of bias tool. Results: Out of 3,186 papers, 38 randomized clinical trials (8 related to gingivitis therapy, 20 related to nonsurgical periodontal therapy, and 10 related to surgical periodontal therapy) were finally included in the review. The outcomes were categorized as primary (that answered the focus question) and secondary (regarding additional quality characteristics). The adjunct use of HA combined to all treatment modalities shows improvement of patients’ postoperative course, in terms of decreased inflammatory reactions, and changes in periodontal pocket depth and clinical attachment level. No side effects were reported in any of the included studies. Among the secondary outcomes were the variety of HA formulations and chemical forms, the variety in application, follow-up protocol and blinding design, the uneven geographic distribution of the studies, and the low bibliometric characteristics of most studies. Conclusion: Overall and despite the positive effects reported, further research is needed to define the ideal HA compound, formulation, and regimen characteristics for periodontal disease treatment. Clinical significance: The adjunct use of HA may lead in the reduction of the prescription of nonsteroid anti-inflammatory drugs and achieve improved clinical parameters, including periodontal probing depth, periodontal inflammation, and clinical attachment level.
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