Understanding the Printing Dynamics during Inkjetting of Cell-Laden Bioink for 3D Biomanufacturing Applications

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Inkjet printing, where droplets of liquid are deposited onto a substrate in a computer-controlled pattern, is one of the most promising technologies for creation of 3D living tissues and organs. The adopted carrier fluid, referred to as bioink, incorporates living cells. Due to cell-cell interaction, living cells adhere to each other in the print nozzle to form cell aggregates. These aggregates can clog the nozzle or result in unplanned droplets deposited on the substrate, both of which can significantly affect inkjet printing reliability. This project involves fundamental scientific research to understand the mechanisms of living cell adhesion and aggregation during inkjet printing, and how to control the printing outcomes. If successful, this research can bridge jet-based bioprinting manufacturing science and biomedical applications, open new avenues in regeneration of 3D functional tissues and organs, and significantly advance the U.S. healthcare industry. The research outcomes will be seamlessly integrated into a biomanufacturing course currently offered in the Manufacturing Engineering and Bioengineering programs to increase participation of female and minority students. The research will also be disseminated through the regional summer camp (Explore Engineering) and national mass media to educate and inspire the general public and the next generation of bioengineers. Engagement of graduate students in the research activities will strengthen the future workforce in bioengineering and advanced manufacturing industries.The research objective is to gain fundamental new knowledge regarding cell aggregation inside the printhead nozzle, and the satellite droplet formation outside the nozzle during inkjet printing of cell-laden bioink. During printing, the bioink is ejected from a piezoelectric printhead to form droplets, which are precisely deposited on the substrate to form 3D constructs layer by layer. It is believed that the nature of pressure wave required to expel the bioink from the nozzle affects both the likelihood of cell aggregation and satellite drop formation. To investigate cell aggregation, cell adhesion will be simulated using a multiphase approach, which models the bioink as a suspension coupling a viscoelastic fluid model with a solid model for living cells. The governing equations for the conservation of mass and momentum will be numerically solved under different excitation voltages and cell concentrations. As the satellite droplet formation depends on the competing actions of ligament radial thinning and axial contraction, both processes will be modeled analytically to predict satellite droplet formation. Once the core fundamentals are understood, the knowledge will be leveraged to generate process phase diagrams in terms of non-dimensional numbers to ultimately identify optimal printing conditions. Additionally, cell viability and proliferation will be assessed immediately after printing and after 7-day incubation to confirm the chosen inkjet printing conditions have no negative impact on the cells. The resulting scientific knowledge is highly adoptable to other biofabrication technologies.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.