Development of a Cell based Bone Forming Construct with BMPTechnology

Large bone defects rarely heal. This is due to several reasons including the severely damaged surrounding environment, insufficient nutritional supply and the lack of a critical number of stem cells required to produce new bone tissue. Standard treatment of these fractures today involve autologous or allograft transplantation, limited by tissue availability, donor site morbidity and potential graft rejection. Subsequently, alternative treatments are required. Natural fracture healing of long bones typically involves the formation of an intermediate cartilaginous-like tissue, called a callus. This quickly formed callus fill the fracture gap and connects the two bone ends to provide mechanical stability. Therefore, in order to develop a more robust treatment for these large bone defects, we propose to take a bioinspired approach by producing a tissue engineered callus construct in vitro, using stem cells. Upon isolation and expansion, these cells can be manipulated in the laboratory to adapt their characteristics and properties, similarly to cells in the natural callus. Next, by incorporating these cells in a matrix/scaffold resembling the native environment, their engineered properties can be sustained. As a last step, the different callusmimetic zones can be assembled to a final construct, which upon transplantation to the bone defect site can continue tissue development while integrating with the two bone ends, leading to successful bridging of the fracture.