Does hyaluronic acid affect hard tissue healing in alveolar bone augmentation procedures? A systematic review of controlled clinical trials

Abstract Objective To provide an overview on the effect of hyaluronic acid (HyA) on hard tissue healing in alveolar bone augmentation procedures in humans (PROSPERO registration: CRD42023464863). Methods Three databases were searched until April 2025. Studies using HyA in any form and in any alveolar bone augmentation procedure were included, if a control group allowing to assess the effect of HyA was available; studies addressing periodontal regeneration or using HyA coated implants were not included. Primary outcome parameters, summarized descriptively, were histologic/radiographic new bone formation (NBF), alveolar ridge width (ARW) and height (ARH). The Cochrane Collaborations RoB 2.0 and ROBINS-I tool were used to assess the risk of bias. Results Fourteen studies with a follow-up of 3–12 months were included, which contributed with 229 patients and 317 sites allowing to assess the effect of HyA. HyA was assessed as adjunct to maxillary sinus floor augmentation (MSFA), guided bone regeneration (GBR), and alveolar ridge preservation (ARP). The addition of HyA significantly improved NBF in 50 and 66% of the MSFA and ARP studies, respectively; however, a significant clinical improvement was not consistently observed. Advantages for NBF as well as ARW or ARH gain have been reported in GBR procedures, but the available data are limited and mostly descriptive. No differences were observed regarding reported post-operative complication rates. Due to the heterogeneity in treatments and outcome measures, as well as the limited number of studies, a meta-analysis was not feasible for any of the outcomes. Conclusions In the original studies, positive and occasionally significant results have been reported for the adjunct use of HyA in alveolar bone augmentation; however, the effect size and clinical relevance is unclear, and further clinical research is needed. Clinical relevance HyA in alveolar bone augmentation is safe, but it remains unclear in which indication and in which application form it may enhance quality and/or quantity of NBF and at what extent.