The clinical efficacy of hyaluronic acid in the treatment of peri-implantitis: a systematic review.

Abstract Background: Hyaluronic acid (HA) is naturally synthesized in the body as a large glycosaminoglycan with roles in hydration, anti-inflammation, regeneration, in addition to cell migration and proliferation. The primary objective of this systematic review was to assess the clinical effectiveness of utilizing HA in the treatment of peri-implantitis on the basis of evidence from clinical studies, including comparisons to placebo or active comparators and observations of clinical interventions. Methods: In accordance with the PRISMA 2020 guidelines, a comprehensive search was conducted across five databases at two different time points to identify randomized and non-randomized controlled trials. Data from six included studies were extracted and analyzed, and then using the Cochrane RoB 2, ROBINS-I, and JBI tools risk of bias was evaluated. The certainty of evidence for key outcomes was graded with the GRADE approach. Results: The review analyzed six studies with follow-up periods ranging from 15 days to 12 months. The findings were heterogeneous. While some studies demonstrated statistically significant improvements in probing pocket depth (PPD) and bleeding on probing (BOP) with adjunctive HA, other studies reported no significant difference compared to controls. Marginal bone loss (MBL) outcomes were particularly inconsistent. The review found that HA had an anti-inflammatory effect by reducing IL-1β levels and showed some benefits against the peri-implantitis associated bacterial community. Conclusion: On the basis of the current evidence, adjunctive HA shows promising effects on clinical parameters such as PPD and BOP and may have a benefit in decreasing levels of early-colonizing bacteria. However, the high degree of heterogeneity in study design, HA formulations, and treatment protocols, coupled with a high risk of bias in many of the included papers, makes it impossible to draw a definitive conclusion. The certainty of evidence for MBL was very low. Subsequent research with standardized, long-term, and well-designed clinical trials is necessary to fully determine HA's role in treating peri-implantitis.