{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:45:34Z","timestamp":1773708334973,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT, COMPETE-FEDER","award":["PEst-C\/SAU\/UI3282\/2013 and UID\/NEU\/04539\/2013"],"award-info":[{"award-number":["PEst-C\/SAU\/UI3282\/2013 and UID\/NEU\/04539\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>(1) Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most often seen side effects in patients treated with nitrogen-containing bisphosphonates (BPs), a post-surgical non-healing wound condition. Since calcium phosphate (CP) compounds are able to adsorb zoledronate (ZOL) when used as a drug delivery vehicle, we aimed to verify if these ceramics might have a potential protective effect for soft tissues surrounding surgical osseous wounds. (2) Methods: The chemical reaction between ZOL and CP compounds was evaluated through ultraviolet-visible spectroscopy and elemental analysis. A primary culture of human gingival fibroblasts (HGF) was established as a model to evaluate the cytotoxicity of the association of ZOL (5\u2013500 \u03bcM) and of ZOL\/biphasic calcium phosphates (BCP). Metabolic activity, cell viability, types of cell death, the cell cycle through, and the migration ability of human gingival fibroblasts were evaluated. (3) Results: ZOL was adsorbed by biphasic calcium phosphate compounds in an aqueous solution. The HGF were sensitive to ZOL toxicity; nevertheless, ZOL\/BCP showed a significant protective effect regarding metabolic activity, cell viability, and cell migration. (4) Conclusions: BCP interaction with ZOL reduces or abolishes its toxicity in HGF. This finding represents a potential solution for BRONJ in the case of patients undergoing therapy with ZOL.<\/jats:p>","DOI":"10.3390\/ma12111840","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T03:56:31Z","timestamp":1559879791000},"page":"1840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-2423","authenticated-orcid":false,"given":"Siri","family":"Paulo","sequence":"first","affiliation":[{"name":"Institute of Endodontics, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0689-6007","authenticated-orcid":false,"given":"Mafalda","family":"Laranjo","sequence":"additional","affiliation":[{"name":"Biophysics Institute, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-7871","authenticated-orcid":false,"given":"Ana M.","family":"Abrantes","sequence":"additional","affiliation":[{"name":"Biophysics Institute, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Jo\u00e3o","family":"Casalta-Lopes","sequence":"additional","affiliation":[{"name":"Biophysics Institute, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Radiation Oncology Department, Coimbra University Hospital Center, 3000-548 Coimbra, Portugal"}]},{"given":"Kathleen","family":"Santos","sequence":"additional","affiliation":[{"name":"Biophysics Institute, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Ana C.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Applied Molecular Biology Unit, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-4173","authenticated-orcid":false,"given":"Anabela Baptista","family":"Paula","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-5417","authenticated-orcid":false,"given":"Carlos Miguel","family":"Marto","sequence":"additional","affiliation":[{"name":"Institute Experimental Pathology, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Ana Bela","family":"Sarmento-Ribeiro","sequence":"additional","affiliation":[{"name":"Applied Molecular Biology Unit, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-5557","authenticated-orcid":false,"given":"Eunice","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Arm\u00e9nio","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Science and Technology University of Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-1650","authenticated-orcid":false,"given":"Maria F.","family":"Botelho","sequence":"additional","affiliation":[{"name":"Biophysics Institute, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI Consortium, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-6161","authenticated-orcid":false,"given":"Manuel M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Endodontics, Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), CNC.IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of Action and Role in Clinical Practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin. 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