Luciana Constantino | FAPESP Agency – Researchers from the Botucatu Biosciences Institute, at the Universidade Estadual Paulista (IBB-Unesp), developed a new biomaterial that accelerates the differentiation of cells that produce bones – known as osteoblasts. The result was promising for future use in bone regeneration processes, and could be used, for example, in grafts and implant coverings.
The study showed that the development of a calcium phosphate – a molecule with a structure similar to bone mineral – loaded (doped) with cobalt is capable of stimulating the differentiation of osteoblasts. The result was published at the Journal of Biomedical Materials Research
“Our data brings together, for the first time, sufficient evidence based on hypoxia [baixa concentração de oxigênio] that we may have a new biomimetic material with prospects for regenerating bone tissue. In grafts there are not always sufficient quantity and quality conditions for the autogenous bone [removido do próprio paciente para enxerto] be used in the clinic”, he tells FAPESP Agency the biologist and professor Willian Fernando Zambuzzi responsible for the study.
Currently, treatments for patients who need grafts, whether due to fractures, interventions to remove tumors (resection) or even dental prosthetics, end up using bone fragments from the individual themselves. This process, however, requires additional surgeries to obtain autogenous material, with an increased risk of infections and longer convalescence time.
Bone biology researcher since the 2000s, Zambuzzi has support from FAPESP and is the advisor of doctoral student Gerson Santos de Almeida, first author of the work. According to the professor, the group has sought to understand molecules and mechanisms involved in bone development and their relationship with biomaterials.
In recent years, with the increase in the population's life expectancy, bone tissue regenerative processes have been the target of research around the world and the search for more effective therapies, aiming to quickly restore the patient, reduce hospitalization time, and the costs of treatment and possible side effects. Among the lines of study are the development of materials that replicate the complexity of the bone structure with similarity, safety and efficiency.
Knowledge construction
In 2014, a study led by researcher Ralf Adams, from the Max Planck Institute (Germany), and published in the magazine Nature showed that endothelial cells – which line blood vessels – have the capacity to stimulate the differentiation of osteoblasts, pointing to synchrony between them. Based on these findings, Zambuzzi, who at the time had support from FAPESP through a Research Assistance – Young Researchers began to develop this line of studies in the then newly created Laboratory of Bioassays and Cellular Dynamics.
Based on previous results added to the literature, the professor worked on the search for molecules that stimulate the growth of blood vessels, aiming for an indirect effect on the differentiation of osteoblasts. He arrived at cobalt chloride (a salt), which is known to stimulate hypoxia and leads the body to increase the number of blood vessels to try to compensate for the lack of oxygen.
“Hypoxia happens naturally in tissues. Knowing its development and the relationship between endothelial cells and bone cells, we enter the biomimetic aspects. From there, we decided to artificially provoke a new molecule – salt doped with cobalt – so that it could stimulate the production of bones, as a complementary effect to the increase in angiogenesis”, explains the professor.
Based on biological evaluation standards (ISO 10993:5), tests showed that there is no toxicity of the new material. Furthermore, the amount of cobalt was decisive in defining the ideal concentration for future biomedical applications, opening new horizons in regenerative medicine. “The results are conclusive in basic research and enable us to seek more complex pre-clinical models of analysis seeking a better translational understanding of these findings, such as animal tests”, says Zambuzzi.
According to the professor, his group has sought to establish biological models in vitro based on the so-called “Principle of 3 R's” – which in Portuguese means reduction, replacement and refinement –, but is convinced of the need for models that preserve the physiology of vertebrates at some stage of the development of new products.
“We are on the path to developing new biomimetic materials that satisfy people's quality of life, giving due ethical importance to the use of experimental animals”, he concludes.
The article Development of cobalt (Co)-doped monetites for bone regeneration can be read at: https://onlinelibrary.wiley.com/doi/10.1002/jbm.b.35319#