Development of hydroxyapatite nanoparticles loaded with folic acid to induce osteoblastic differentiation


Recently it has been shown that folic acid can have an important role in bone regeneration. For this reason, combining a classic bone regeneration system as, hydroxyapatite, loaded with folic acid, may be an important issue to be developed. To address this issue, hydroxyapatite nanoparticles loaded with folic acid were designed as an effective bone regenerative system, to induce osteoblast differentiation and improve the bone regeneration. HapNP were prepared by a hydrothermal method that used citric acid as a tailoring agent of particles morphology and, simultaneously, had the particularly to let carboxylic pendant groups in the particle surface, which provided a platform for the immobilization of folic acid (FA), producing HapNP-FA. A comparative study among hydroxyapatite nanoparticles loaded and unloaded with folic acid in presence of human mesenchymal stem cells was performed. The results demonstrate, that nanoparticles were able to be internalized by human mesenchymal stem cells. In addition, cell proliferation and viability were not affected in a wide concentration range. Both particles induced the expression of Runx2 and the expression and activity of alkaline phosphatase. However, HapNP-FA caused a significantly higher overexpression of Runx2. The osteoblastic differentiation confirms the potential applicability of HapNP-FA in the local bone regeneration. (C) 2016 Elsevier B.V. All rights reserved.



subject category

Pharmacology & Pharmacy


Santos, C; Gomes, P; Duarte, JA; Almeida, MM; Costa, MEV; Fernandes, MH

our authors


The authors would like to acknowledge the financial support of the project by Fundacao para a Ciencia e Tecnologia (FCT) to CQE (UID/QUI/00100/2013).; The authors would like to thanks to Programa Operacional Regional de Lisboa 2020 (Project N. 007317). This work was developed within the scope of the project CICECO- Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement.; This work also received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundacdo para a Ciencia e Tecnologia and Ministerio da Educacao e Ciencia) under the Partnership Agreement PT2020 UID/QUI/50006/2013.

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