{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:31:39Z","timestamp":1786444299642,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry and Research (MUR) National Innovation Ecosystem","award":["ECS00000041-Vitality-CUP D73C22000840006"],"award-info":[{"award-number":["ECS00000041-Vitality-CUP D73C22000840006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Alveolar bone resorption after tooth extraction complicates subsequent dental implant placement. OsteoBiol\u00ae GTO\u00ae (Tecnoss\u00ae, Giaveno, Italy) is an innovative pre-hydrated heterologous collagenated bone mix blended with a thermosensitive copolymer (OsteoBiol\u00ae 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\u00ae GTO\u00ae 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\u00ae GTO\u00ae 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\u00ae GTO\u00ae 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.<\/jats:p>","DOI":"10.3390\/bioengineering13080907","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:11:16Z","timestamp":1786439476000},"page":"907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pro-Angiogenic Response to OsteoBiol\u00ae GTO\u00ae in an In Vitro Endothelial Cell Model Is Associated with Modulation of the COX-2\/PGE2\/VEGF Axis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9033-0104","authenticated-orcid":false,"given":"Alessia","family":"Ricci","sequence":"first","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4868-3838","authenticated-orcid":false,"given":"Tea","family":"Romasco","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8042-6009","authenticated-orcid":false,"given":"Marwa","family":"Balaha","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Piattelli","sequence":"additional","affiliation":[{"name":"School of Dentistry, UniCamillus-Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy"},{"name":"Facultad de Medicina, UCAM Universidad Cat\u00f3lica San Antonio de Murcia, 30107 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Cataldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-2116","authenticated-orcid":false,"given":"Natalia Di","family":"Pietro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Imaging and Clinical Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-6943","authenticated-orcid":false,"given":"Susi","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Udeabor, S.E., Heselich, A., Al-Maawi, S., Alqahtani, A.F., Sader, R., and Ghanaati, S. 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