Scaffolds for bone repair using computer aided design and manufacture

Abstract

Defects in bone are a constant and serious problem. They occur as a result of high energy trauma, congenital conditions or are created surgically to treat bone tumours or infection. Currently the treatment for these conditions is awkward for the patient, takes a long time and has a high complication rate. An elegant solution would be to mend the bone defect using the patient own cells; osteoblasts or mesenchymal stem cells seeded onto a supportive material scaffold. For successful regeneration of bone structures, a scaffold production technique has to be adopted that can precisely control porosity, internal pore architecture and fibre thickness, as well as maximising media diffusion and optimising scaffold mechanical properties so that the scaffold can withstand bone bearing pressures. It would also be beneficial if the scaffold uniformly distributed surface strain along the fibres throughout the entire scaffold as this would encourage more even cell proliferation/differentiation in the structure. This was addressed by performing a series of finite element analyses on the computer aided design model where the mechanical properties of the natural or synthetic polymer used have been incorporated to yield an accurate strain profile of the entire scaffold. The process used here to generate the scaffolds is a Rapid Prototyping method that creates a three-dimensional object through the repetitive deposition of fibres in layers via extrusion. Due to the high accuracy and versatility of the extruder, the diameter of the pores can be precisely controlled to an accuracy of 10μm, in the manufactured scaffolds the pore size ranges from 100 to 300μm as that is what is found in trabecular bone. Natural and synthetic polymers were plotted which altered the biodegradability properties of the scaffold and the degrees of cell adhesion, proliferation and differentiation in the structure. Scaffolds were manufactured that demonstrated compatibility with cell adhesion, proliferation and osteogenic differentiation. On completion of the scaffolds, the latter were seeded with osteoblasts or marrow stromal cells and put into a mechanically stimulating bioreactor machine to induce a small strain in the scaffold; this was performed to encourage cell proliferation/differentiation. The structure was left until the osteoblasts or marrow stromal cells modified the scaffold through bone deposition. In-vivo experiments were then undertaken. Preliminary data indicated an effect of mechanical stimulation of the cell/scaffold construct on the degree of mineralization of cell matrix generated by human osteogenic cells.