Regenerating large bone defects is a great challenge in regenerative medicine. Embryonic stem cell (ESC) therapies are an attractive option due to their unlimited proliferation and ability to produce the cell types needed for bone repair. Here, we propose creating a three-dimensional alginate hydrogel that displays bioactive epitopes and has mechanical properties that induce osteogenic differentiation of ESCs and increase bone formation in vitro. We will do this by building upon previous research in the group of Prof Molly Stevens, which found that ESCs cultured on the extracellular matrix of bone forming osteoblasts increased both differentiation into osteogenic cells and bone formation. We propose using a proteomic approach to identify the proteins that are responsible for this effect. Once the proteins are known, they will be cut into short overlapping peptides that will be synthesized and attached to a cell culture surface. ESCs will then be grown on them to determine the sequences that induce osteogenesis. Using two-dimensional hydrogels of different stiffness that are coated with the osteogenic peptide, the mechanical properties that maximize osteogenesis will be determined. This peptide will then be coupled to alginate to form a hydrogel whose mechanical properties will be tailored to maximize bone formation. Novel sequences which induce osteogenesis are important to stem cell biology and an artificial matrix that differentiates ESCs into osteoblasts using both displayed ligands and stiffness would be important to regenerative medicine. The project Peptide Osteogel will be beneficial to Europe by bringing a scientist with a unique skill set into a top biomaterials lab to work on a multidisciplinary project that will increase the quality and status of science in the European Union. This fellowship will enable greater collaboration and transfer of knowledge across Europe, increasing the mobility and human potential of scientists across the continent.
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