Large-scale cell expansion is one of the bottlenecks in tissue biofabrication. Typically, there are 109 cells in one gram of tissue. However, the number of replicating cells harvested from a donor is extremely low (~105 cells), which necessitates approximately 10,000-fold cell expansion for clinical applications. The National Cell Manufacturing Consortium (NCMC) roadmap lists cell expansion equipment as an unmet industrial need for cost-effective, large-scale cell expansion. The conventional 2D planar T-flask method for cell culture is difficult to scale-up. The manual process using the T-flask is labor-intensive, susceptible to contamination, and requires high cost to meet CGMP cell manufacturing standards. Commercially available 3D cell expansion devices based on stacked plates, microcarriers, and hollow fibers also have several limitations, including limited scalability, lack of critical process control, high shear stress, large nutrition gradient, and complex downstream processing.
This project, jointly funded by Advanced Regenerative Manufacturing Institute (ARMI/BiofabUSA), is to develop a novel cell expansion bioreactor system (patent pending) that is expected to overcome the limitations of the current cell expansion devices on the market. In this application, the prototypes of three different scales of the bioreactors and a matched perfusion system will be developed. The bioreactor system will be validated by the expansion of four different cell types by multiple potential users. The proposed cell expansion bioreactor is expected to be a module, integrated well into BioFabUSA’s entire tissue biofabrication system, and provide ARMI members a new tool to perform cell expansion for different tissue manufacturing applications.
To date, SwRI has designed and fabricated three different sized bioreactors and designed and assembled a perfusion controller system that works with the three bioreactors. At present, we are verifying the bioreactors and perfusion systems.