Multi-variant bioreactor for cartilage tissue engineering

Articular cartilage is a stratified tissue with distinct layers expressing different protein types/amounts and having different cell morphologies. Research on articular cartilage has shown that compression, hydrostatic pressure, and hypoxic conditions tend to give the articular cartilage the properties of the middle and bottom layers of the natural tissue, while surface motion and normoxic conditions induce a superficial zone cartilage phenotype. Our objective is to build a bioreactor that can control all of these parameters in order to test for different values and find optimal ranges to create an engineered cartilage tissue with ideal characteristics. Thus we built a four-chamber bioreactor that can apply hydrostatic pressure, compression, shear and torsion, in addition to controlling oxygen tension supplied to the cartilage. The mechanical simulation is applied using a gear-rack mechanism having a frequency of 0.5Hz. The oxygen tension is controlled by electric valves connected to O2 and N2 bottles coming to the bioreactor's chambers, oxygen and pressure sensors are used in the process. The bioreactor is controlled and coded using Arduino software. After building the bioreactor, a Matlab computer vision test was done to check for the precision of the mechanism, and finally injurious and proliferation tests were performed to check for the effectiveness of the bioreactor. Results of the precision testing showed a 4% error for a 1mm displacement. Results of the injurious tests showed significant numbers of dead cells for compressive forces larger than 10 MPa. In conclusion, our newly developed system is capable of delivering a variety of mechanical stimuli and oxygen tension simulating those in native cartilage. The importance of this system lies in its applicability to cartilage but also to other mechanoresponsive and oxygen sensitive tissues such as bone, muscle, tendons, ligaments, and blood vessels. In the future, we plan to improve our bioreactor by using a cam-follower mechanism for higher precision.