Pro-Angiogenic Response to OsteoBiol® GTO® in an In Vitro Endothelial Cell Model Is Associated with Modulation of the COX-2/PGE2/VEGF Axis

Alveolar bone resorption after tooth extraction complicates subsequent dental implant placement. OsteoBiol® GTO® (Tecnoss®, Giaveno, Italy) is an innovative pre-hydrated heterologous collagenated bone mix blended with a thermosensitive copolymer (OsteoBiol® TSV Gel) that has demonstrated osteoconductive properties. Despite direct contact with blood vessels upon socket filling, its pro-angiogenic potential has not been directly investigated on endothelial cells. Thus, in this study, an in vitro model, consisting of the EA.hy926 endothelial cell line exposed to different OsteoBiol® GTO® soaking preparations [original soaking (OS), centrifuged soaking (CS), and diluted soaking (DS)] at multiple concentrations (1, 5, 10, and 20 mg/mL) was established to identify optimal experimental conditions and characterize the underlying molecular mechanisms. Cell viability and collagen release quantification led to the selection of 10 mg/mL OS as the most suitable condition. Under this condition, OsteoBiol® GTO® induces an early increase in Cyclooxygenase-2 (COX-2) protein expression and Prostaglandin E-2 (PGE2) secretion, followed by upregulation of Vascular Endothelial Growth Factor (VEGF) protein expression and phosphorylation of Endothelial Nitric Oxide Synthase (eNOS) at serine 1177. The tube formation assay confirmed the pro-angiogenic functional outcome. These results suggest an association between the pro-angiogenic response of endothelial cells to OsteoBiol® GTO® and modulation of the COX-2/PGE2/VEGF axis. This effect could be attributed to collagen accumulation in the OS, thereby representing a novel and promising pro-angiogenic mechanism with potential implications for wound healing and guided bone regeneration following tooth extraction.