A Cost-effective Bioreactor to Advance Functional Tissue Engineering of Cartilage

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the leading cause of chronic disability in the United States. A clinical goal in the treatment and prevention of OA is to develo replacement cartilage using tissue engineering (TE) technologies.Although TE cartilage currently lacks the mechanical resilience of native cartilage, the mechanical properties of TE constructs can be enhanced by applying chemical and mechanical stimuli during culture. To speed the discovery of optimal stimulation protocols, research platforms need to be available that enable fast, clear and reliable communication of functional outcomes (i.e. mechanical properties). Towards this goal, we introduce a compact six-station bioreactor that combines the efficiency of batch testing with the accuracy normally reserved for dedicated single-specimen material test systems. In the highly successful phase I feasibility study, an innovative method was proven to deliver accurate dynamic stimulations and evaluate mechanical properties insix stations. This technology can now be incorporated into a multi-axial frame that uses hybrid and adaptive controls to maximize testing efficiency and flexibility. The first three aims of this application are to 1) increase throughput, 2) add loading modalities and 3) automate performance and analysis tools. The effect of these modifications on mechanical accuracy will be verified using external sensors and imaging methods. Hydrogels and bovine cartilage will be tested in the high- throughput bioreactor and a conventional single-station test system to validate the bioreactors automated measurement of mechanical properties. System robustness will be determined by quantifying the effect of operating the bioreactor for millions of cycles. In the fourth aim,bioreactor prototypes will be distributed to three cartilage TE laboratories to evaluate and optimize the bioreactor prior to commercial launch. Successful completion of the study aims will provide an efficient, reliable and flexible research platform to advance the development and clinical transfer of cartilage TE technology. PUBLIC HEALTH RELEVANCE: Tissue engineering of articular cartilage presents a promising strategy for treatment of osteoarthritis, a debilitating and prevalent disease. Cartilage engineering techniques, however, are currently unable to reproduce the mechanical properties critical to native cartilage, thus impeding the transfer of TE technology to patient care. A bioreactor is therefore proposed to facilitate the rapid discovery of mechanical conditions that promote the biosynthesis of mechanically viable tissue.