Gallic acid released by a layered double hydroxide-coated scaffold of hydroxyapatite and β-tricalcium phosphate inhibits the osteoclast formation In Vitro.

Following dental extraction, alveolar bone loss, driven by the osteoclast (OC) bone-eroding cells, is a relevant concern in dental practice since it could compromise the possibility of installing dental implants. This study aimed to develop a drug delivery system releasing the antiosteoclastogenic molecule gallic acid (GA) at the alveolar bone level to control the dysregulated balance between OCs and bone-building osteoblasts and thus delay bone erosion. We functionalized small blocks of the hydroxyapatite- and β-tricalcium phosphate-based RIGENERA BTK BCP biomaterial with layered double hydroxide (LDH) and GA (RIG_LDH-GA). By the in vitro model of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL)-induced osteoclastogenesis in RAW 264.7 macrophages, we demonstrated that the conditioned medium (CM) obtained after 1-day incubation with RIG_LDH-GA contrasts the OC formation in a dose-dependent manner until a complete inhibition at the highest tested dose, while the unfunctionalized control (RIG) is ineffective. TRAP enzyme activity, OC marker gene expression, and bone resorption activity confirmed the antiosteoclastogenic effect of RIG_LDH-GA CM. Moreover, the expression of RANK (the RANKL's receptor), otherwise induced by RANKL treatment, was reduced to the untreated control extent, consistent with the decreased expression of the transcription factors c-Fos and NFATc1, activated downstream in the RANK signaling pathway and inducing RANK itself. Thus, since GA released by the RIG_LDH-GA system effectively exerted an antiosteoclastogenic effect, RIGENERA BTK BCP functionalization with LDH and GA likely appears to be an osteoprotective upgrade of this biomaterial, already possessing bone regenerative properties, and might find successful clinical application in preventing osteoclast-mediated alveolar bone loss.