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Strontium-containing nanoparticles and their versatility for biomaterials fabrication: implications and applications in biomineralization


Biominerals are commonly found in nature in the form of hybrid organic-inorganic compounds, in which the organic portion is mainly composed by proteins and polyssacharides. On it is turn, the in the inorganic portion carbonates and phosphates can be found, mainly as hydroxyapatite (HAp) and silica. The process by which these exquisite minerals are formed is named biomineralization and can serve as natural inspiration for the synthesis of biomimetic biomaterials ready to the applied in vivo. A classic example of this process is the formation of bone and teeth in the vertebrates. Bone is a hybrid material composed mainly by non-stoichiometric HAp, called biological apatite, and type-I collagen. The complex process by which bone tissue is formed has been described in the literature under a biological point-of view considering the enzymatic mechanism involved in the formation of matrix vesicles secreted from bone cells, and under an inorganic point-of-view that considers the supersaturation of the physiological media, mainly in calcium and phosphate, for the HAp precipitation guided by type-I collagen fibrils. The intersection point between these two models is the need of a tridimensional confined media that favors the nucleation of crystals by local supersaturation guided by an organic matrix. The complete elucidation of this process is far to be accomplished, and more than the biological interest, the understanding of bone formation delivers useful information for the fabrication of biomaterial applied for bone substitution and regeneration.Biological apatite has low crystallinity and differs from synthetic HAp also in the stoichiometry, in special, due to the ionic substitutions observed in the physiological media. In special, phosphate ions are mainly replaced by carbonate. Cationic substitutions are also observed. Mg2+, Zn2+ e Sr2+ are the main substitutes of Ca2+ found in the biological apatite. In the present project, we are focused in the importance of Sr2+ substitution and its role in the fabrication of new biomaterials. The main source of Sr2+ in living organisms is the oral dietary. A regular dietary contains 2-4 mg of Sr2+/day, coming from vegetables and cereals. As consequence of the similarity of the Ca2+ and Sr2+ ionic radius, this trace element in the human body, is accumulated mainly in the bone tissue. Sr2+ is found in young bone, which stimulates the study of the influence of this ion in the bone formation process, and thus in osteoconductive biomaterials fabrication. The role of Sr2+ in the osteoblasts activity has been demonstrated. However, the mechanisms that lead to the different cellular stimulus and the changes in the bone tissue properties have been low explored. In this sense, the present proposal put together basic aspects related to the composition and structure of biomimetic HAp precipitated in the presence of Sr2+, and the further building of biomaterials using these particles. Compounds containing Sr2+ will be tested in the dentistry field for the dental hypersensitivity treatment, and also as bone regenerating promoters. At the final, the effect of these biomaterials in the activity of cells important for the bone formation process will be investigated throughout a molecular point-of-view. The expression of the genes assigned to the production of the main proteins involved in bone formation will be investigated in order to evaluate the pathway by which these biominerals guide the cells activity, as detailed in the main text of the proposal. (AU)

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Scientific publications (12)
(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)
TOMAZELA, LARISSA; EUFRASIO CRUZ, MARCOS ANTONIO; NASCIMENTO, LARISSA AINE; FAGUNDES, CECILIA C.; DA VEIGA, MARCIA ANDREIA MESQUITA S.; ZAMARIOLI, ARIANE; BOTTINI, MASSIMO; CIANCAGLINI, PIETRO; BRASSESCO, MARIA SOL; ENGEL, EDGARD E.; et al. abrication and characterization of a bioactive polymethylmethacrylate-based porous cement loaded with strontium/calcium apatite nanoparticle. Journal of Biomedical Materials Research Part A, v. 110, n. 4, . (19/25054-2, 17/26742-4)
VESCHI, EKEVELINY AMABILE; BOLEAN, MAYTE; DA SILVA ANDRILLI, LUIZ HENRIQUE; SEBINELLI, HEITOR GOBBI; STRZELECKA-KILISZEK, AGNIESZKA; BANDOROWICZ-PIKULA, JOANNA; PIKULA, SLAWOMIR; GRANJON, THIERRY; MEBAREK, SAIDA; MAGNE, DAVID; et al. Mineralization Profile of Annexin A6-Harbouring Proteoliposomes: Shedding Light on the Role of Annexin A6 on Matrix Vesicle-Mediated Mineralization. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 16, p. 15-pg., . (19/25054-2, 21/13140-1, 17/20846-2, 19/08568-2, 22/05026-7)
ANDRILLI, LUIZ H. S.; SEBINELLI, HEITOR G.; FAVARIN, BRUNO Z.; CRUZ, MARCOS A. E.; RAMOS, ANA PAULA; BOLEAN, MAYTE; MILLAN, JOSE LUIS; BOTTINI, MASSIMO; CIANCAGLINI, PIETRO. NPP1 and TNAP hydrolyze ATP synergistically during biomineralization. PURINERGIC SIGNALLING, v. N/A, p. 14-pg., . (19/25054-2, 19/08568-2, 21/13140-1, 17/20846-2)
NOGUEIRA, LUCAS FABRICIO BAHIA; EUFRASIO CRUZ, MARCOS ANTONIO; AGUILAR, GUILHERME JOSE; TAPIA-BLACIDO, DELIA RITA; DA SILVA FERREIRA, MARCIA ELIANA; MANIGLIA, BIANCA CHIEREGATO; BOTTINI, MASSIMO; CIANCAGLINI, PIETRO; RAMOS, ANA PAULA. Synthesis of Antibacterial Hybrid Hydroxyapatite/Collagen/Polysaccharide Bioactive Membranes and Their Effect on Osteoblast Culture. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 13, p. 22-pg., . (18/25871-8, 20/08727-0, 16/25955-1, 19/25054-2, 21/05947-2)
SILVA, LUCAS SANTOS; DE MELO, MARYANNE TRAFANI; SPONCHIADO, PEDRO AUGUSTO INVERNIZZI; BARBOSA JUNIOR, FERNANDO; TAPIA-BLACIDO, DELIA RITA; CIANCAGLINI, PIETRO; RAMOS, ANA PAULA; MANIGLIA, BIANCA CHIEREGATO. Synthesis of composite corn starch/hydroxyapatite nanoparticle biomembranes and their effect on mineralization by osteoblasts. Journal of Applied Polymer Science, v. 140, n. 43, p. 14-pg., . (19/08568-2, 21/08359-4, 20/08727-0, 19/25054-2, 21/05947-2)
CODOGNATO, D. C. K.; PENA, F. S.; DOS REIS, E. R.; RAMOS, A. P.; BORISSEVITCH, I. E.. Effects of serum albumin on the photophysical characteristics of synthetic and endogenous protoporphyrin IX. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, p. 12-pg., . (19/25054-2)
D.C.K. CODOGNATO; F.S. PENA; E.R. DOS REIS; A.P. RAMOS; I.E. BORISSEVITCH. Effects of serum albumin on the photophysical characteristics of synthetic and endogenous protoporphyrin IX. Brazilian Journal of Medical and Biological Research, v. 55, . (19/25054-2)
NOGUEIRA, LUCAS FABRICIO BAHIA; CRUZ, MARCOS ANTONIO EUFRASIO; MELO, MARYANNE TRAFANI DE; MANIGLIA, BIANCA CHIEREGATO; CAROLEO, FABRIZIO; PAOLESSE, ROBERTO; LOPES, HELENA BACHA; BELOTI, MARCIO M.; CIANCAGLINI, PIETRO; RAMOS, ANA PAULA; et al. Collagen/Kappa-Carrageenan-Based Scaffolds as Biomimetic Constructs for In Vitro Bone Mineralization Studies. Biomacromolecules, v. 24, n. 3, p. 9-pg., . (19/08568-2, 20/08727-0, 22/01219-5, 19/25054-2, 16/25955-1, 18/25871-8, 21/05947-2)
SEBINELLI, HEITOR GOBBI; ANDRILLI, LUIZ HENRIQUE SILVA; FAVARIN, BRUNO ZOCCARATTO; CRUZ, MARCOS AANTONIO EUFRASIO; BOLEAN, MAYTE; FIORE, MICHELE; CHIEFFO, CAROLINA; MAGNE, DAVID; MAGRINI, ANDREA; RAMOS, ANA PAULA; et al. Shedding Light on the Role of Na,K-ATPase as a Phosphatase during Matrix-Vesicle-Mediated Mineralization. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 23, p. 19-pg., . (19/25054-2, 21/13140-1, 17/20846-2, 19/08568-2, 22/05026-7)
NOGUEIRA, LUCAS FABRICIO BAHIA; CRUZ, MARCOS ANTONIO EUFRASIO; TOVANI, CAMILA BUSSOLA; LOPES, HELENA BACHA; BELOTI, MARCIO MATEUS; CIANCAGLINI, PIETRO; BOTTINI, MASSIMO; RAMOS, ANA PAULA. Curcumin-loaded carrageenan nanoparticles: Fabrication, characterization, and assessment of the effects on osteoblasts mineralization. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 217, p. 9-pg., . (19/25054-2, 19/08568-2, 18/25871-8)
NOGUEIRA, LUCAS FABRICIO BAHIA; MANIGLIA, BIANCA C.; BUCHET, RENE; MILLAN, JOSE LUIS; CIANCAGLINI, PIETRO; BOTTINI, MASSIMO; RAMOS, ANA PAULA. hree-dimensional cell-laden collagen scaffolds: From biochemistry to bone bioengineerin. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, v. 110, n. 4, . (19/08568-2, 20/08727-0, 19/25054-2, 18/25871-8)

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