Osteochondral Tissue Engineering

A major challenge in engineering grafts with hierarchical structure, composition and mechanical properties starting from a single cell preparation, is the design of an appropriate bioreactor system. In addition to the nutrient transport to cells in clinically sized constructs, a bioreactor should provide lineage-specific biological stimuli in various regions of the graft. For stratified cartilage-bone grafts, the development of mechanical competence necessitates the application of biophysical stimuli, which is technically challenging particularly for anatomically shaped constructs.

Our lab has begun studies to generate mechanically competent, biological grafts (such as the temporomandibular joint) using anatomically correct scaffolds seeded with human mesenchymal stem cells (hMSCs). To accommodate these grafts, we are developing a bioreactor capable of coordinating biological, physiological and mechanical stimuli, and applying them in a spatially and temporally controlled manner to provide lineage-specific stimulation within the cartilage and bone regions. This includes the use of chondro-inductive growth factors and dynamic stimulation to the cartilage regions of the graft, and osteo-inductive factors combined with medium perfusion (for nutrient transfer and shear stress) in the bone phase of the graft. The combined stimuli should be applied while the two phases are being grown in apposition to stimulate osteochondral integration.