A nontoxic strontium nanoparticle that holds the potential to act upon osteocompetent cells: An in vitro and in vivo characterization

Author:

Hayann Larwsk1,da Rocha Vitor Freire2,Cândido Marina Ferreira3,Vicente Raphael Martini4,Andrilli Luiz H. S.1,Fukada Sandra Y.5,Brassesco María Sol4,Ciancaglini Pietro1,Engel Edgard Eduard2,Ramos Ana Paula1ORCID

Affiliation:

1. Department of Chemistry, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto University of São Paulo Ribeirão Preto Brazil

2. Department of Orthopedics and Anesthesiology, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto Brazil

3. Department of Genetics, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto Brazil

4. Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto University of São Paulo Ribeirão Preto Brazil

5. School of Pharmaceutical Sciences of Ribeirao Preto University of São Paulo Ribeirão Preto Brazil

Abstract

AbstractEstrogen deficiency, long‐term immobilization, and/or aging are commonly related to bone mass loss, thus increasing the risk of fractures. One option for bone replacement in injuries caused by either traumas or pathologies is the use of orthopedic cement based on polymethylmethacrylate (PMMA). Nevertheless, its reduced bioactivity may induce long‐term detachment from the host tissue, resulting in the failure of the implant. In view of this problem, we developed an alternative PMMA‐based porous cement (pPMMA) that favors cell invasion and improves osteointegration with better biocompatibility. The cement composition was changed by adding bioactive strontium‐nanoparticles that mimic the structure of bone apatite. The nanoparticles were characterized regarding their physical–chemical properties, and their effects on osteoblasts and osteoclast cultures were assessed. Initial in vivo tests were also performed using 16 New Zealand rabbits as animal models, in which the pPMMA‐cement containing the strontium nanoparticles were implanted. We showed that the apatite nanoparticles in which 90% of Ca2+ ions were substituted by Sr2+ (NanoSr 90%) upregulated TNAP activity and increased matrix mineralization. Moreover, at the molecular level, NanoSr 90% upregulated the mRNA expression levels of, Sp7, and OCN. Runx2 was increased at both mRNA and protein levels. In parallel, in vivo tests revealed that pPMMA‐cement containing NanoSr 90%, upregulated two markers of bone maturation, OCN and BMP2, as well as the formation of apatite minerals after implantation in the femur of rabbits. The overall data support that strontium nanoparticles hold the potential to up‐regulate mineralization in osteoblasts when associated with synthetic biomaterials.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Wiley

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