Biofabrication of New Composite Scaffolds for Bone Tissue Engineering Applications

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Recent reviews have highlighted the major potential of electrospun nanofibers for various tissue engineering applications. The proposed research program aims to fabricate new biodegradable composite scaffolds for bone tissue engineering applications using electrospinning technologies and hydrogels. The physical characteristics (composition, architecture, pore size, etc.) of melt electrospun poly(e-caprolactone) (PCL) meshes will first be optimized to promote osteoprogenitor cell attachment and differentiation. Endothelial cells and growth factors, delivered in a controlled manner using fibrin-alginate hydrogels, will then be incorporated into the PCL meshes (previously seeded with osteoprogenitor cells) to promote vascularization. Indeed, a major challenge for bone repair is to provide an environment that promotes not only bone mineralization, but also vascularization. Research will be segmented as follows: Objective 1: Fabricate mineralized poly(e-caprolactone) (PCL) meshes with specific physical characteristics by using melt electrospinning, surface modification, and osteoprogenitor cells. PCL meshes with different pore sizes will be melt electrospun, coated with calcium phosphate (CaP) and characterized by scanning electron microscopy and energy dispersive X-ray spectroscopy. Osteoprogenitor cells will then be cultured on the mesh surface for mineralization.Objective 2: Determine the biological and mechanical properties of the mineralized PCL meshes (developed in Objective 1) combined with fibrin-alginate hydrogels loaded with vascular endothelial growth factor (VEGF)-165 and endothelial cells, under perfused conditions. SEM, quantification of alkaline phosphatase, confocal microscopy, immunocytochemistry, histology/immunohistochemistry, and mechanical testing will be performed to evaluate the biological and mechanical properties of the constructs.The proposed research uses cutting-edge technology to fabricate new mineralized and vascularized bone substitutes. Autologous bone grafts are often used to heal critical-size bone defects, but the use of bone substitutes presents an alternative to this invasive technique. However, current bone substitutes are still facing significant limitations including insufficient supply, high cost and the inability of the substitutes to integrate with the surrounding host tissue. The proposed research will therefore provide tangible benefits to the Canadian health-care system. In addition, it will potentially lead to new and patentable products and/or processes eventually transferable for commercialization. Finally, this research will only be possible by recruiting highly qualified team members, who will be exposed to state-of-the-art technologies and will have a unique opportunity to acquire multidisciplinary training at the interface between fundamental and applied research.