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

Siri Paulo; Mafalda Laranjo; Ana  M. Abrantes; João Casalta-Lopes; Kathleen Santos; Ana  C. Gonçalves; Anabela  Baptista Paula; Carlos  Miguel Marto; Ana  Bela Sarmento-Ribeiro; Eunice Carrilho; Arménio Serra; Maria  F. Botelho; Manuel  M. Ferreira

doi:10.3390/ma12111840

Materials (Jun 2019)

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

Siri Paulo,
Mafalda Laranjo,
Ana M. Abrantes,
João Casalta-Lopes,
Kathleen Santos,
Ana C. Gonçalves,
Anabela Baptista Paula,
Carlos Miguel Marto,
Ana Bela Sarmento-Ribeiro,
Eunice Carrilho,
Arménio Serra,
Maria F. Botelho,
Manuel M. Ferreira

Affiliations

Siri Paulo: 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
Mafalda Laranjo: 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
Ana M. Abrantes: 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
João Casalta-Lopes: 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
Kathleen Santos: 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
Ana C. Gonçalves: 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
Anabela Baptista Paula: 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
Carlos Miguel Marto: 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
Ana Bela Sarmento-Ribeiro: 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
Eunice Carrilho: 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
Arménio Serra: Department of Chemical Engineering, Faculty of Science and Technology University of Coimbra, Polo II, Pinhal de Marrocos, 3030-790 Coimbra, Portugal
Maria F. Botelho: 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
Manuel M. Ferreira: 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

DOI: https://doi.org/10.3390/ma12111840
Journal volume & issue: Vol. 12, no. 11
p. 1840

Abstract

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(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.

Published in Materials

ISSN: 1996-1944 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering; Technology: Engineering (General). Civil engineering (General); Science: Natural history (General): Microscopy; Science: Physics: Descriptive and experimental mechanics
Website: http://www.mdpi.com/journal/materials/

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