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

Abstract

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)