Biomineralization potential of inorganic polymer for bone tissue regenerative engineering

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Biomineralization potential of inorganic polymer for bone tissue regenerative engineering Project Abstract Bone grafting is the second most common tissue transplantation procedure, with 2.2 million procedures being conducted worldwide. The clinical gold standard for treating large non-healing craniofacial defects is to harvest and transplant autogenous grafts. However, the supply of autogenous grafts is limited, and post-surgery morbidities are frequent. Due to a reliance on titanium-based, polymer-based, and ceramic-based orthopaedic implants, standard synthetic bone scaffolds often result in complications such as infection or bone degeneration due to a mismatch in both geometry and physical properties between the implant and the surrounding natural bone structure. Therefore, there is a gap of knowledge in novel multiscale materials for tissue regenerative engineering to mitigate bone loss, and promote bone proliferation around the host bone structure. The long- term research goal is to discover novel multiscale bone scaffolds by integrating composite materials science, physical sciences, and translational medicine. My long-term career goal is to enable tissue fabrication for bone regeneration through the integration of advanced materials science, physical sciences, and translational medicine. I plan to focus on a new class of materials, inorganic polymers that are synthesized at low temperatures by dissolving an aluminosilicate source in an alkali-silicate solution. My research hypothesis is inorganic polymer materials can be used to mimic the multiscale microstructure and mechanical behavior of compact bone and induce bone regeneration thanks to their nanoscale structure, mesoporosity, and excellent mechanical properties. Nanoscale structural features are frequently linked to improved osseointegrativity whereas as micropores promote cell migration, vascularization and innervation. My preliminary results have shown that the pore size and total porosity of inorganic polymer composites can be modified by adjusting the mix design and the processing route. Unreinforced pure inorganic polymer exhibits stiffness and strength values close to that of compact bone, suggesting that a closer match in mechanical properties can be obtained through materials design. My work has shown that inorganic polymer, is biocompatible with mouse fibroblast cells and human mesenchymal cells. However, what is yet unknown are the cell-wall interactions, the osteoblast mineralization mechanisms, and the in-vivo performance for inorganic polymer scaffolds. Therefore, this discovery has laid the groundwork to move to translational regenerative bioengineering to elucidate the factors driving the biocompatibility of novel engineered inorganic polymer-based scaffold. Two specific research aims are proposed. Aim One will yield optimized synthesis routes for biocompatible inorganic polymer-based bone scaffolds with a fundamental understanding of the mechanisms of cell attachment and migration in inorganic polymer scaffolds. Aim Two will enable a fundamental understanding of osteoblast differentiation and mineralization mechanisms in inorganic polymer nanocomposites. Aim Three will investigate the potential of inorganic polymer scaffolds to accelerate the healing of complex craniofacial defects in-vivo using rat animal models. The proposed RO3 project will yield novel materials for bone tissue regenerative engineering.