Clinical efficacy of hyaluronic acid in peri-implantitis treatment: a systematic review of clinical, radiographic, and biological outcomes

Objective: This systematic review evaluated the impact of adjunctive hyaluronic acid (HA) on outcomes in the management of peri-implantitis, while characterizing the various protocols and formulations. Materials and methods: In accordance with the PRISMA 2020 guidelines, a search was conducted across five databases up to February 10, 2025 to identify randomized controlled trials (RCTs) and non-randomized clinical studies including controlled studies and case series. A dual-pass screening and data extraction process was employed to ensure data accuracy. The risk of bias was evaluated using Cochrane Risk of Bias 2, Risk of Bias in Non-Randomized Studies of Interventions-I, and Joanna Briggs Institute tools. The certainty of evidence for key outcomes was graded with the GRADE approach. Results: Six studies (four RCTs, one controlled pilot study with a split-mouth design, and one prospective case series) with 110 patients were included; sample sizes ranged from 5 to 63 participants, and follow-up periods ranged 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), other studies reported no significant difference compared to controls. Marginal bone loss (MBL) outcomes were inconsistent. HA demonstrated an anti-inflammatory effect by reducing interleukin-1 beta levels and showed some benefits against the peri-implantitis-associated bacterial community. Conclusion: Adjunctive HA is associated with favorable effects on PPD and BOP, but with a low certainty of evidence, and may have a benefit in decreasing the levels of early-colonizing bacteria. Significant improvement in MBL was associated only with surgical approaches but with a very low certainty of evidence. The high degree of heterogeneity in study design, HA formulations, and treatment protocols, coupled with a high risk of bias, makes it difficult to draw a definitive conclusion. Well-designed RCTs are required to establish the clinical role of HA in the management of peri-implantitis.