An innovative approach to osteopenia-associated bone repair using a drug delivery system of injectable hydrogels incorporated with bioglass functionalized with raloxifene and strontium ranelate

Abstract

The aim of this present study will be to evaluate drug delivery systems using injectable hydrogels incorporated with bioglass particles functionalized with osteoporosis drugs in in vitro osteogenesis, as well as in the regeneration of critical bone defects in the femurs of ovariectomized rats. The drugs used to functionalize the bioglass particles will be raloxifene and strontium ranelate. First, the synthesis and characterization of bioglass will be carried out, followed by its functionalization with drugs, through the sonochemical route. In sequence, the characterization of the hydrogels incorporated with the bioglasses functionalized with the drugs will be carried out. The in vitro tests will be performed using differentiated mesenchymal cells in osteoblasts isolated from the femurs of ovariectomized rats. Cell activity and differentiation will be evaluated by analyzing cell viability, total protein content, alkaline phosphatase activity, formation of mineralization nodules and genotoxicity. The in vivo experiments will be performed using young adult female Wistar rats (n=8 for each group and subgroup) that will undergo bilateral ovariectomy (OVX) or sham bilateral ovariectomy (Sham). To ensure that the rats selected for the experiments are cycling normally, an evaluation of the estrous cycle of these rats will be performed by means of exfoliative cytology and they will be monitored for clinical changes such as eating habits, hair loss, activities in general, infection of surgical wounds and hair loss. of weight. After 8 weeks of the OXV and Sham surgeries, critical bone defects will be performed in the distal epiphysis of the femurs bilaterally, which will be filled with the clot group and with the experimental groups: a) injectable hydrogel incorporated with bioglass particles functionalized with the drug raloxifene (BRx) b) injectable hydrogel incorporated with bioglass particles functionalized with the drug strontium ranelate (BSr). The animals will be euthanized 4 weeks after the surgical procedure, at which time 10mL of blood will be removed from each animal for cytokine analysis. After euthanasia, the left femurs will be submitted to computerized microtomography analysis for the morphometric evaluation of the bone formed in the critical defect. While the right femurs will be submitted to laboratory processing for histological and histomorphometric analysis. To verify the presence of systemic side effects, a descriptive histological evaluation of the heart, liver and skin tissue located in the area adjacent to the surgical wound will be performed. The quantitative data will be submitted to the normality test for the selection of the appropriate statistical test (parametric or non-parametric), with a significance level of 5%.