Efficient Optimization And Scale-Up Production Of Human IPSC Aggregates And Organoids For Bioprinting

By Debbie L. L. Ho, Stacey Lee, Mark A. Skylar-Scott, Jianyi Du, Tony Tam, Soham Sinha, Sean Devine, Art Hamfeldt, Jonathan D. Weiss, Hope T. Leng, Danielle Klinger, Mengdi He, Donald Traul, Jessica E. Herrmann, Lee G. Fradkin, Tze Kai Tan, Quentin Vicard, Kishore Katikireddy, Rukmini Ladi, Noushin Dianat, David Standish, Peter Tomasello, Shanya Jiang, Gaurav Kaushik, Rohit Saklecha, and Maya Fuerstenau-Sharp

Bioprinting for clinical-scale tissue and organ manufacturing necessitates processes capable of generating clinically relevant quantities of hiPSCs. These cells must also be able to form organoids that can differentiate into a variety of cell types, making them suitable as functional bioinks. The objective of this study was to identify the optimal cell culture conditions to yield high cell density and maintain high cell viability while ensuring consistent aggregate morphology and expression of pluripotency markers.

To address this, a multi-disciplinary approach was employed that integrated computational software with automated and scalable bioreactor systems. The refined conditions and specialized media were subsequently evaluated in a larger-scale stirred-tank bioreactor to determine the feasibility of direct scaling of this process.