Nontechnical Abstract This project supported by the Biomaterials program in the Materials Research Division is to develop a novel material called Rolled Scaffold (RS) and to build a next generation of bioreactors based on RS for large-scale cell culture. With recent progress in biotechnology, animal cells are used to produce protein-based drugs and diagnostic antibodies. Also, stem cells are investigated as effective cures for degenerative diseases that are previously incurable. These applications require large-scale bioreactors with higher efficiency and reliability than currently available ones. The unique microstructure of RS provides very high surface-area to volume ratio and allows efficient flow of culture media through it, making RS ideal material for high-density adherent culture. Unlike conventional bioreactors, the bioreactor based on RS separates the cells from the culture media reservoir, allowing sufficient aeration of media and removal of cellular bio-waste without cellular damages. These improvements are expected to significantly reduce the production cost in biopharmaceutical industries and facilitate the introduction of exciting clinical applications of stem cells.
Suspension culture in stirred tank bioreactors are widely used to culture animal cells in large scale. However, harmful hydrodynamic shear stress and insufficient mass transfer rate of nutrients and gases limit efficiency and reliability of suspension culture in large scale. In this project, PI aims to develop novel RS bioreactors to overcome inherent limitations of suspension culture. RS is a thin polymer film with spacers that are rolled into a cylinder containing numerous identical microfluidic channels. Cells are growing in inner surfaces of RS and culture media flows through the microfluidic channels in a laminar flow. The RS can provide very large cell culture area and high mass transfer rate of nutrients and gases with minimal shear stress. In addition, separation of cells from media reservoir allows novel configurations of RS-based bioreactors. PI plans (1) to develop a mass-production setup of RS, (2) to develop a dialysis RS-bioreactor that can effectively remove cellular waste from the media for efficient production of therapeutic proteins, and (3) to implement a RS-bioreactor with low-temperature media storage that can extend lifetime of heat-sensitive signaling molecules in culture media for affordable stem cell production. Besides, this project seeks to develop self-sustainable STEM curriculum for high school, to promote STEM literacy among young students through various outreach activities, and to train graduate and undergraduate student into future workforce in biomaterials area through active research participation with priorities to female and underrepresented groups in STEM.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
