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Exploring the synergistic effect between collagen and Sr2+ in bone mineralization

Grant number: 17/24827-2
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): March 03, 2018
Effective date (End): March 02, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
Principal Investigator:Ana Paula Ramos
Grantee:Camila Bussola Tovani
Supervisor abroad: Nadine Nassif
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Université Pierre et Marie Curie (Paris 6), France  
Associated to the scholarship:14/24249-0 - Association of osteogenic proteins in biominerals and metallic oxides doped with rare-earth: interaction with membrane models systems, BP.DD


The inorganic compounds present in living organisms are formed by a complex mechanism (biomineralization) which involves steps of nucleation and growth within a confined space. The need of design new bone replacement materials has driven several studies towards the process of bone formation. Bone is a hybrid material formed of plate-like non-stoichiometric hydroxyapatite (HAp) crystals and collagen fibrils. The collagen matrix plays a pivotal role on bone Hap formation acting as a confined media to the crystals growth, which in turn grows parallel to the long axis of collagen fibrils. PO43- lattice substitution is another effect responsible for the properties of bone HAp such as its poorly crystallized and calcium-deficient nature. Cations substitution is also observed in bone HAp lattice. A common substitution is the Ca2+ replacement by Sr2+ due to their charge to size ratio similarity. As a consequence, Sr, a trace element in human body widely available in soil and drinking water, accumulates preferentially in the skeleton. The fact of Sr2+ be found mostly in young bone tissues has driven several studies aiming to understand its biological role in the process of bone tissue formation and consequently its application as osteoconductive systems. Moreover, recently it was demonstrated that not only the cellular metabolism, but also the mechanical properties of bone tissue are affected by anti-osteoporotic drugs containing Sr2+ such as strontium ranelate. Nevertheless, few studies have dealt with the mechanism involved in the bone mineralization in the presence of Sr2+. In this regard, we propose the use of two approaches to study the synergism between collagen and Sr2+ in the bone HAp formation. Firstly, we will adopt an approach developed by Nassif and coworkers in which collagen connement was used to precipitate a large variety of apatite models to study the effect of Sr2+ substitutions on biological HAp formation and bone disorders. In a second moment, we will use polycarbonate membranes with controlled pores-size to design Sr-HAp particles containing collagen, and at the same time to study the mechanism of HAp formation. It will be evaluated the influence of different Sr2+ concentrations, the presence of an organic matrix and the confinement on HAp physical and chemical properties, such as its poorly crystallized nature. Those materials will be characterized by several techniques which allow an investigation at the nanoscale, such as energy electron loss spectroscopy (EELS), cryogenic transmission electron microscopy, 31P solid state resonance magnetic spectroscopy, electron diffraction, and Raman spectroscopy. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TOVANI, CAMILA BUSSOLA; GLOTER, ALEXANDRE; AZAIS, THIERRY; SELMANE, MOHAMED; RAMOS, ANA P.; NASSIF, NADINE. Formation of stable strontium-rich amorphous calcium phosphate: Possible effects on bone mineral. Acta Biomaterialia, v. 92, p. 315-324, JUL 1 2019. Web of Science Citations: 2.

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