Hyaluronic acid versus enamel matrix derivative for periodontal regeneration in intrabony defects: a systematic review and meta-analysis

Abstract

Periodontitis can lead to the formation of intrabony defects. Enamel matrix derivative (EMD) is a well-established biomaterial for regeneration. Currently, hyaluronic acid (HA) has emerged as a promising alternative with anti-inflammatory and osteoinductive properties. This meta-analysis compares the clinical efficacy of HA and EMD in the regenerative treatment of periodontal intrabony defects. In December 2025, we conducted a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library for randomized and non-randomized controlled trials directly comparing HA to EMD in patients with periodontitis and intrabony defects. The primary outcomes were clinical attachment level (CAL) and probing pocket depth (PPD). For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1 + 563. We included four studies with a total of 167 defects in 156 patients. There were no statistically significant differences between HA and EMD in CAL at 6 months (MD = 0.08 mm, 95% CI − 0.37; 0.54, P = 0.72), 12 months (MD = 0.51 mm, 95% CI − 0.08; 1.11, P = 0.09), or 18 months (MD = 0.53 mm, 95% CI − 0.17; 1.24, P = 0.14). Similarly, we found no significant differences in PPD at 6 months, although heterogeneity was high at longer follow-ups. HA showed a significant reduction in gingival recession (REC) at 12 months only with comparable findings at 6 and 18 months. Also, no differences were found in bleeding on probing (BOP). HA has comparable efficacy to EMD with similar improvement in CAL and PPD following regenerative surgery for intrabony defects over 6 to 18 months. However, our findings are limited by the small number of included studies and heterogeneity in treatment protocols. Future large-scale, standardized clinical trials with long-term follow-up are warranted.