EAGER: Synergistic Influences of Oscillating Pressure and Growth Factor on Chondrogenesis in a Novel Centrifugal Bioreactor

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1212573/ Van WieCartilage regenerative medicine for osteoarthritis will be advanced signifi-cantly by improved fundamental understanding at the cellular level of the complex interplay of mechanical and biochemical stimuli needed to create healthy cartilage. The central hypothesis posed by these investigators is that optimal differentiation of human mesenchymal stem cells (hMSCs) occurs via exposure to bioactive molecules combined with physical stimuli that promote membrane N-cadherin de-pendent cellular junctions. The researchers investigate our hypothesis using a unique continuous centrif-ugal bioreactor (CCBR) in this industry-university collaborative EAGER project. Intellectual Merit:The strength of this research program is the collaborative interface between biology, engineering and technology. WSU engineers will provide the novel bioreactor and AFM analytical technology, and REGN scientists will provide genetics and cell biology expertise. The research is : 1) to grow and differentiate hMSCs in the CCBR; 2) to determine the addi-tive and synergistic influences of multiple stimuli on chondrogenesis; and 3) to establish the relative contributions and synergistic impacts of various stimuli on mRNA upregulation and expression of proteins responsible for signaling pathways and mechano-transduction mechanisms responsible for heightened chondrogenic differentiation of hMSCs. The work could yield potential commercial application for autologous chondrocyte tissue culture systems for regenerative implants. Broader impact:Teaching & training: Presentations will be given on synergistic stimuli on chondrogenesis at REGN, and annual NIH Protein Biotechnology Training Program symposia; Representation: A U.S. woman and/or minority PhD student is being recruited to join the pro-gram through an anticipated NSF Graduate Research Supplement; Infrastructure: A new CCBR will be developed capable of imparting multiple stimuli for mechanotransduction studies; Dissemination at AIChE and ACS meetings and in technical journals; Societal Benefits: The work is expected to have long-term impact on regenerative cartilage repair and other tissue culture applications that impact human health.