title: Development of hydroxyapatite nanoparticles loaded with folic acid to induce osteoblastic differentiation.
abstract: 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.
authors.affiliation: EST Setúbal, DEM, Instituto Politécnico de Setúbal, Campus IPS, 2914-508 Setúbal, Portugal; CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: Catarina.santos@estsetubal.ips.pt.
authors.forename: Catarina
authors.initials: C
authors.lastname: Santos
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, Porto, Portugal; REQUIMTE/LAQV, U. Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gomes
authors.affiliation: CIAFEL, Faculdade de Desporto, Universidade do Porto, Portugal.
authors.forename: José A
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: Department of Materials and Ceramic Engineering, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Margarida M
authors.initials: MM
authors.lastname: Almeida
authors.affiliation: Department of Materials and Ceramic Engineering, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Maria E V
authors.initials: ME
authors.lastname: Costa
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, Porto, Portugal; REQUIMTE/LAQV, U. Porto, Porto, Portugal.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Fernandes
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019343:Citric Acid / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry*; D005492:Folic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D053758:Nanoparticles; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*
chemical_list: D019343:Citric Acid; D017886:Durapatite; D005492:Folic Acid; D000469:Alkaline Phosphatase
keywords: Bone regeneration; Folic acid; Nanohydroxyapatite; Osteoblastic induction