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Title: Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw
Authors: Paulo, Siri 
Laranjo, Mafalda 
Abrantes, Ana M. 
Casalta-Lopes, João 
Santos, Kathleen 
Gonçalves, Ana C. 
Paula, Anabela Baptista 
Marto, Carlos Miguel 
Ribeiro, Ana Bela Sarmento 
Carrilho, Eunice 
Serra, Arménio C. 
Botelho, Maria F. 
Ferreira, Manuel M. 
Keywords: biomaterials; biomineralization; bisphosphonate-related osteonecrosis of the jaw; cellular biology; gingival fibroblasts; osteonecrosis; zoledronate
Issue Date: 6-Jun-2019
Publisher: MDPI
Project: FCT, COMPETE-FEDER (Strategic Project PEst-C/SAU/UI3282/2013 and UID/NEU/04539/2013) 
Serial title, monograph or event: Materials
Volume: 12
Issue: 11
Abstract: (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.
ISSN: 1996-1944
DOI: 10.3390/ma12111840
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais

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