Featured paper: Promising composite biomaterial for regeneration of bone tissue.


[Paper: Assisted deposition of nano-hydroxyapatite onto exfoliated carbon nanotube oxide scaffolds. Hudson Zanin, Cintia M. R. Rosa, Noam Eliaz, Paul W. May, Fernanda Roberta Marciano and Anderson O. Lobo. Nanoscale, v. 7, p. 10218-10232, 2015. DOI: 10.1039/C4NR07317G]

In a study conducted by the Laboratory of Biomedical Nanotechnology (NANOBIO) from the Brazilian University of Vale do Paraíba (UniVap), in a partnership with scientists from the Brazilian National Institute for Space Research (INPE) and universities from Israel and the UK, a biomaterial was produced that advanced the understanding of some stages on the generation of bone tissue in vitro (out of the real biological context). The low cost material has the potential to be used to accelerate the regeneration of bone tissue in vivo – which may be useful in case of bone fractures, for example. The results of the study were recently published on the scientific journal Nanoscale, from the Royal Society of Chemistry.

In broad terms, the natural generation of bone tissue occurs when cells called osteoblasts produce the organic part of bones to later cover it with the inorganic part, the hydroxyapatite – chemical formula Ca5(PO4)3(OH). The natural deposition of hydroxyapatite is a biomineralization process (production of minerals by living organisms). The biomineralization is not yet fully understood, but its comprehension is of great importance for the development of applications aiming to create bone tissue or firm implants into bones.

“The paper contributes to the understanding of the precipitation process of carbonated hydroxyapatite in vitro, for short amounts of time, over three-dimensional surfaces based on nanohydroxyapatite, vertically aligned carbon nanotubes and graphene”, says Professor Anderson de Oliveira Lobo, Biomedical Engineer with master’s and doctoral degrees in Materials Physics and Chemistry, who signs the paper as its corresponding author.

In association with the Diamonds and Related Materials (DIMARE) group from INPE, represented by researcher Evaldo José Corat, the NANOBIO team, coordinated by Professors Anderson de Oliveira Lobo and Fernanda Roberta Marciano, produced scaffolds with vertically aligned carbon nanotubes. The nanotubes underwent a process of surface oxidation by the plasma etching technique, which exfoliated their tips, produced graphene oxide and thus created a more favorable environment for the formation of nanohydroxyapatite nuclei in the following production stage of the material, the electrodeposition.  This deposition technique was chosen because, among the known methods, it produces the artificial apatite most similar to the biological one, in terms of microstructure and dimensions. In order to set the electrodeposition parameters by means of electrochemical studies, the researchers from Brazil requested the collaboration of a specialist on the subject at a global level, scientist Noam Eliaz, from the University of TelAviv. After the electrodeposition, the team obtained a composite material which retained the biological properties of hydroxyapatite, with the advantage that the presence of the carbon nanotubes reinforced the hardness and resistance of the material.

Afterwards, the scientists submerged the material in simulated body fluid (a liquid that simulates the conditions of blood plasma and is commonly used in biomaterials studies). Under these conditions, the composite material, which is bioactive in this kind of liquid, spontaneously formed a layer of carbonated hydroxyapatite, which, jointly with the nanotubes scaffold and hydroxyapatite films, produced a new composite material.

The researchers were able to observe and study the whole process of biomineralization within periods of up to 7 days, and, in the paper, they propose models to explain several stages.  At that moment, more precisely in the discussion on the chemical modelling of how the biomineralization of the composite occurs, it was important to count with the participation of researcher Paul May, from the University of Bristol, jointly with Hudson Zanin, researcher from the Laboratory of Energy Supply and Distribution from UniVap, who was conducting postdoctoral studies in the British university.

Schematics showing the whole production process of nanobiomaterials and the in vitro bioactivity assay. At the top, from left to right, there is: (i) the production of vertically aligned carbon nanotubes, (ii) exfoliation for the exposition of graphene sheets, (iii) a diagram displaying the nanohydroxyapatite electrodeposition process (iv). On the two middle lines it is demonstrated the whole process of biomineralization in vitro, showing how exchanges between cations and anions occur, up to the formation of the carbonated nanohydroxyapatite layer. On the last line, there are micrographs showing the process of biomineralization at the starting time (right after incubation) and after 7 days (last micrograph).

The research went beyond bringing advances to the understanding of biomineralization in vitro. “The comprehension of this in vitro process may be associated to the process of in vivo regeneration of these materials”, says Professor Anderson Lobo. “In vitro studies with human osteoblastic cells and in vivo assays using animals are being carried out by graduate students and postdoctoral fellows at UniVap’s NANOBIO”, he adds.

The origins of the study is found in Lobo’s doctoral research, carried out at the Brazilian Technological Institute of Aeronautics (ITA) and defended in 2011, in which he managed, for the first time, to synthesize composites with vertically aligned carbon nanorods and nanohydroxyapatite. The research counted or counts with the financial support of Brazilian research funding agencies FAPESP, CNPq, FINEP and CAPES.