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Open AccessArticle

Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw

1
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
2
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
3
Radiation Oncology Department, Coimbra University Hospital Center, 3000-548 Coimbra, Portugal
4
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
5
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
6
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
7
Department of Chemical Engineering, Faculty of Science and Technology University of Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra, Portugal
*
Author to whom correspondence should be addressed.
Materials 2019, 12(11), 1840; https://doi.org/10.3390/ma12111840
Received: 14 May 2019 / Revised: 3 June 2019 / Accepted: 4 June 2019 / Published: 6 June 2019
(This article belongs to the Special Issue Biomaterials for Dental Healing)
(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 (5–500 μM) 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. View Full-Text
Keywords: biomaterials; biomineralization; bisphosphonate-related osteonecrosis of the jaw; cellular biology; gingival fibroblasts; osteonecrosis; zoledronate biomaterials; biomineralization; bisphosphonate-related osteonecrosis of the jaw; cellular biology; gingival fibroblasts; osteonecrosis; zoledronate
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Paulo, S.; Laranjo, M.; Abrantes, A.M.; Casalta-Lopes, J.; Santos, K.; Gonçalves, A.C.; Paula, A.B.; Marto, C.M.; Sarmento-Ribeiro, A.B.; Carrilho, E.; Serra, A.; Botelho, M.F.; Ferreira, M.M. Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw. Materials 2019, 12, 1840.

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