Synergistic efficacy of a biomimetic hydroxyapatite-citrate complex for dentin hypersensitivity: an in vitro and clinical study

To evaluate the synergistic effect of a novel Hydroxyapatite (HAP)-Citrate complex toothpaste on dentinal tubule occlusion and the relief of dentine hypersensitivity (DH). For the in vitro study, thirty bovine dentin discs were randomly divided into three groups with ten specimens each: group A, a test toothpaste (HAP, potassium citrate and NaF), group B, a control toothpaste (HAP and NaF), and group C, a placebo toothpaste (NaF only). After 3 and 7 days of simulated brushing, tubule occlusion and mineralized layer formation was assessed using Scanning electron microscopy (SEM). A 12-week, double-blind, randomized trial involving 129 subjects compared the test toothpaste to a bioactive glass-based positive control toothpaste and a placebo. The severity of DH, indicated by Schiff (air) and Yeaple (tactile), was evaluated at baseline, 2, 6, 8, and 12 weeks, with the last 4 weeks being a washout period. Data were analyzed using ANOVA to compare differences between groups, with a significance level set at p < 0.05. In the in-vitro study, the HAP-Citrate complex toothpaste demonstrated rapid and effective occlusion. After 3 and 7 days, it achieved a dentinal tubule occlusion rate of 96.0 ± 2.1% and 99.7 ± 0.7%, significantly surpassing the placebo group (43.5 ± 10.1% and 76.4 ± 7.3%, respectively; p < 0.05). Notably, the HAP-Citrate complex exhibited superior deep-sealing capabilities compared to the standard HAP control toothpaste. At day 7, the HAP-Citrate group showed an intratubular occlusion depth of more than 40 μm (vs. 13 μm in the HAP control) and formed a surface mineralized layer of more than 5 μm thick (vs. 1 μm in the HAP control). In the clinical trial, the HAP-citrate toothpaste showed significant DH relief, with Schiff and Yeaple score improvements of 21.39% and 100.85% respectively at 8 weeks compared to placebo (p < 0.05), comparable to the positive control. Notably, the reduction in air-stimulus sensitivity was sustained at the 12-week follow-up, four weeks after the subjects discontinued the product use. The novel HAP-citrate complex toothpaste can build deep, protective mineral seal on dentin tubules. Its clinically proven performance makes it a superior, science-backed choice for effective sensitivity management. Chinese Clinical Trial Registry, TRN: ChiCTR2500115399, Registration date: 25 December 2025.