Hyaluronic acid in tooth extraction: a systematic review and meta-analysis of preclinical and clinical trials

Objectives To assess whether in animals or patients with ≥ 1 tooth extracted, hyaluronic acid (HyA) application results in superior healing and/or improved complication management compared to any other treatment or no treatment. Materials and methods Three databases were searched until April 2022. The most relevant eligibility criteria were (1) local application of HyA as adjunct to tooth extraction or as treatment of alveolar osteitis, and (2) reporting of clinical, radiographic, histological, or patient-reported data. New bone formation and/or quality were considered main outcome parameters in preclinical studies, while pain, swelling, and trismus were defined as main outcome parameters in clinical studies. Results Five preclinical and 22 clinical studies (1062 patients at final evaluation) were included. In preclinical trials, HyA was applied into the extraction socket. Although a positive effect of HyA was seen in all individual studies on bone formation, this effect was not confirmed by meta-analysis. In clinical studies, HyA was applied into the extraction socket or used as spray or mouthwash. HyA application after non-surgical extraction of normally erupted teeth may have a positive effect on soft tissue healing. Based on meta-analyses, HyA application after surgical removal of lower third molars (LM3) resulted in significant reduction in pain perception 7 days postoperatively compared to either no additional wound manipulation or the application of a placebo/carrier. Early post-operative pain, trismus, and extent of swelling were unaffected. Conclusions HyA application may have a positive effect in pain reduction after LM3 removal, but not after extraction of normally erupted teeth. Clinical relevance HyA application may have a positive effect in pain reduction after surgical LM3 removal, but it does not seem to have any impact on other complications or after extraction of normally erupted teeth. Furthermore, it seems not to reduce post-extraction alveolar ridge modeling, even though preclinical studies show enhanced bone formation.