Author(s):
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.
Date: 2019
Persistent ID: https://hdl.handle.net/10316/107149
Origin: Estudo Geral - Universidade de Coimbra
Project/scholarship:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/PT;
Subject(s): biomaterials; biomineralization; bisphosphonate-related osteonecrosis of the jaw; cellular biology; gingival fibroblasts; osteonecrosis; zoledronate
Description
(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.
