Efficacy of adjunctive use of hyaluronic acid in surgical and nonsurgical periodontal treatment. A systematic review and meta‐analysis

Background: High interest has been recently shown toward the use of hyaluronic acid (HA) gel as adjuvant to nonsurgical but also to surgical periodontal therapy. Aim: To update the knowledge on the potential clinical effects of HA when used in conjunction with nonsurgical and surgical (both regenerative and mucogingival) periodontal therapy by applying the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Materials and Methods: Three different PICOS frameworks were used to guide the inclusion of eligible studies dealing with the adjunctive application of HA in nonsurgical, surgical periodontal therapy, and in root coverage procedures. The following variables were considered: clinical attachment level gain (CALgain), pocket depth reduction (PPDred), recession reduction, pocket closure (for nonsurgical), bleeding score (for nonsurgical), bone gain (for surgical and nonsurgical), percentage of root coverage (%RC, for root coverage procedures). A detailed systematic search was conducted in the following targeted electronic databases: Medline via Pubmed, EMBASE, Cochrane Database of Systematic Reviews and Scielo. Studies were grouped into three predefined analytical strata corresponding to nonsurgical therapy, surgical periodontal therapy, and mucogingival procedures, allowing separate meta-analyses tailored to each clinical scenario. Risk of Bias assessment was performed by using the RoB 2.0 Tool and the overall strength of the available evidence was determined by using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: From 1554 records, 31 studies were included in the systematic review, but only 20 were eligible for meta-analysis. In nonsurgical periodontal therapy, the adjunctive application of HA showed an overall statistically significant improvement in terms of CALgain (difference of 0.72 mm, 15 studies), PPDred (difference of 0.57 mm, 16 studies), and bone gain (difference of 0.56 mm, 2 studies). However, when only studies at low risk of bias were considered, the statistically significant difference was not confirmed. No statistically significant differences were observed for recession reduction, pocket closure and bleeding score. In surgical periodontal therapy, two studies suggested greater CALgain (difference of 1.36 mm, 2 studies) and PPDred (difference of 1.03 mm, 2 studies) with adjunctive HA, though both trials were at unclear risk of bias. For mucogingival procedures, two studies showed a modest increase in %RC RC (difference of 15.29%, 2 studies), while no benefit was found for other clinical parameters. Conclusions: Within its limitations, the present analysis shows that the adjunctive use of HA produces variable clinical effects across periodontal therapies. Small improvements are observed in nonsurgical treatment, and limited data suggest a potentially favorable effect in periodontal healing. Overall, the current evidence does not allow definitive clinical recommendations, and further well-designed trials are needed to clarify the therapeutic role of HA.