Strategies for the improvement of bone/implant interface in the presence of systemic impairment: from lab bench to clinics: translational studies

Abstract

This project has the principal aim on evaluation of strategies that are related to the installation device (implants) that allow the improvement of repair bone in the presence of systemic condition, in pre-clinical, in vivo studies. The systemic impairment condition that will be focused on this study are osteoporosis, developed in ovariectomized rats and type 2 diabetes, developed in male rats after association of cafeteria diet and streptozotocin low doses injection. The choice of both conditions is justified by the high prevalence of them in world population. The strategies that will be proposed extend from macrogeometry of implants to the use of drug delivery system with the development of coatings (layer by layer technique) with biomolecules that through local action are able to trigger cellular responses that improve the perimplantar repair process. The proposed strategies will be individualized for each comorbid studied. In the osteoporosis condition, the change of macrogeometry will be evaluated with the use of implants that have porous in medium third, mimetizing bone trabeculae. Besides this, biomolecules will be used in the drug delivery system (layer by layer) and that are related to the osteoblastic activity stimulous after osteocalcin production activation (K2 vitamin) or liberating Wnt/Beta catenin pathway (anti sclerostin antibody). In the type 2 Diabetes condition, considering the high quantity of metabolic changes promoved by this pathology, it will be added to the strategies, the systemic administration of the phytoterapic Bauhinia Forficata that through its hypoglycemic effect, it will favor the systemic condition of the animals during the whole experiment. Modifications of implant will be performed through coatings (layer by layer) of biomolecule that act in cellular level, favoring immunological responses (calcitriol as active form of vitamin D3). Preliminary tests will be performed in order to validate the surfaces through cell culture tests. After this, in vivo analysis will be performed with the aim to characterize the bone/implante interface through the following analysis: biomechanical, histological, immunohistochemical, molecular, micro CT and ultrastructural. The analysis of mineral precipitation will be performed with fluorochromes and visualization with confocal microscopy. All of the data will be submitted to statistical analysis. (AU)