"From Bioinspiration to Innovation: Repertoire of Physiostructural Bioactive Molecules of Bone as a Guide for the Development of Biomimetic Products"

Abstract

Despite appearing static, bone tissue is highly dynamic, with a recognized capacity for remodeling and regeneration throughout the lifespan of vertebrates, an activity controlled by the coupling between osteoblasts and osteoclasts. In cases of extensive and critical-sized lesions, the need for support material arises to contribute to tissue repair/regeneration events, requiring the clinical use of biomaterials such as calcium phosphates, which play a crucial role in regenerative medicine due to their exceptional properties. These materials, chemically similar to bone tissue components, create a favorable environment for cell proliferation and differentiation, crucial for the regeneration of tissues damaged or lost due to injuries, diseases, or aging. Additionally, calcium phosphates can be designed to be biocompatible and biodegradable, being well tolerated by the body and integrated into the tissue over time. The present project aims to develop doped calcium phosphates for bone regeneration, with potential application as bone filling materials, coatings for metallic elements, or hydrogels. To identify which elements are suitable for doping, mice will be used in STAGE I, where embryonic bone will be collected during endochondral ossification development for proteomic analysis, RNA sequencing, and chemical element analysis, including their concentrations. With the data obtained, calcium phosphates will be synthesized and subjected to physicochemical characterization, followed by in vitro tests of biocompatibility, gene and protein expression, zymography, and mineralization assays in osteoblastic cells, comprising STAGE II. In STAGE III, in vivo assays will be conducted to understand the osteo-regenerative capacity of the proposed new construct, using mice subjected to biological tests described in the literature. Furthermore, there is interest in applying for a complementary BEPE scholarship for a sandwich internship, through a partnership with Prof. João Mano, University of Aveiro, Portugal, with whom collaboration began in 2024, aiming to develop preliminary synthesis and combination protocols, optimizing the application of the biomaterial in bone tissue injuries. It is worth noting that the candidate, Dr. Gerson, carried out synthesis and characterization methodologies of chitosan-based hydrogels in Canada, when working with the group of Prof. Diego Mantovani at Laval University. The project will use the structure already assembled with resources from the JP-FAPESP grant (2014/22689-3) and the current Regular Project (FAPESP: 2022/15157-1).