Hyaluronic acid for peri-implantitis: promising biology, not yet a standard adjunct

Peri-implantitis remains one of the most challenging complications in implant dentistry, and the search for effective adjunctive therapies continues to drive clinical research. This systematic review by Khayat examines whether hyaluronic acid (HA), when used as an adjunct to conventional treatment, improves clinical, radiographic, and biological outcomes in patients with peri-implantitis.

Following PRISMA 2020 guidelines, the author searched five databases through February 2025, identifying six eligible studies — four randomized controlled trials (RCTs), one controlled split-mouth pilot study, and one prospective case series — totaling 110 patients. Sample sizes were small, ranging from 5 to 63 participants, and follow-up periods varied widely, from 15 days to 12 months. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and JBI tools, while the certainty of evidence was graded according to the GRADE framework.

The findings present a mixed picture. Several studies reported statistically significant reductions in probing pocket depth (PPD) and bleeding on probing (BOP) in HA-treated sites, suggesting a clinically meaningful anti-inflammatory effect. This is further supported by reductions in interleukin-1β levels, a key mediator of peri-implant inflammation, and by some evidence of activity against early-colonizing bacterial species. However, marginal bone loss (MBL) outcomes were inconsistent: significant radiographic improvement was observed only in studies incorporating a surgical approach, and the certainty of this evidence was rated as very low. Across the board, heterogeneity in HA formulations, molecular weights, delivery methods, and treatment protocols makes cross-study comparison difficult and limits the strength of any pooled interpretation.

From a clinical standpoint, the take-home message is one of cautious optimism. HA appears to offer a genuine, if modest, benefit in reducing soft-tissue inflammation around implants — particularly when integrated into a structured treatment protocol. Its biological plausibility is solid: HA modulates inflammatory cascades, supports tissue healing, and may interfere with early biofilm colonization. Yet the evidence base is too heterogeneous and underpowered to support definitive clinical recommendations. The low-to-very-low GRADE certainty ratings underscore how premature it would be to establish HA as a standard adjunct in peri-implantitis management.

For periodontists and implantologists, this review signals both a direction and a gap. HA is a biologically rational adjunct, and its safety profile is well established. But without larger, well-designed RCTs with standardized protocols, consistent HA formulations, and longer follow-up periods, its precise role in the peri-implantitis treatment armamentarium cannot be defined. Clinicians may consider its use as part of a comprehensive non-surgical or surgical protocol, while remaining aware that the current evidence does not yet justify a change in standard-of-care recommendations.