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Development of cells co-culture models to assess the effect of new strontium and flavonoids complexes with application in bone and cartilage regeneration

Grant number: 23/07244-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): September 01, 2023
Effective date (End): August 31, 2025
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
Principal Investigator:Ana Paula Ramos
Grantee:Gildacio Pereira Chaves Filho
Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

The demographic displacement of population aging and the appearance of chronic diseases can affect the regenerative capacities of tissues, including bone and cartilage tissue. These problems trigger the search for biomaterials able to support the regenerations and healing of these tissues. In this perspective, the use of strontium and flavonoids for bone and cartilagerelated therapies have attracted the attention, since they combine osteophilic, osteinductive and anti-inflammatory properties. However, a very important step in the screening of new drugs is the model used to assess biological effects. To date, there are no studies in the literature evaluating the effect of complexes composed of strontium and flavonoids in co-culture models composed of bone, immune and cartilage cells, which could be very promising to understand what happens in a more reliable model of the bone/cartilage microenvironment. For instance, it has been shown that strontium has an stimulating effect on osteoblasts and inhibition effect on osteoclasts activity, however there is no data on the simultaneous effects on both the cells. Furthermore, the use of co-culture system models in scientific research emerge as sustainable model to screening of new molecules/complexes or biomaterials for, reducing steps for posterior in vivo studies. Taken together, the present proposal aims to develop different coculture models composed of osteoblasts, macrophages, chondrocytes and progenitor cells to screening and study the potential of new complexes of strontium and flavonoids carried by typeI and type II collagen to (1) promote osteogenic differentiation and bone formation in a in vitro co-culture model composed of osteoblasts and osteoclasts; (2) promote osteogenesis and immunomodulatory potential in a in vitro co-culture composed of osteoblasts and macrophages for bone regeneration, and (3) promote modulation of chondrogenesis in a in vitro co-culture system composed of chondrocytes and mesenchymal progenitor cells. The complexes with best in vitro activity will be selected for in vivo studies.

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