Developing a 3D Printed High-density Adherent Scaffold Architecture for Large-scale Cardiomyocyte Production

Abstract

The scalable production of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a major barrier to their translation as a regenerative therapy for myocardial infarction. Bioreactors like the stirred-tank system are commonly used for large-scale hPSC-CM manufacturing; however these populations typically display an immature phenotype. While maturation can be improved on 2D substrates, conventional 2D formats are not readily amenable to producing billions of cardiomyocytes required for therapeutic applications. Here, we pursued the fabrication of a scalable 3D printed high-density adherent scaffold (HDAS) array for hPSC- CM production. We found that fusion deposition modelling could generate compact scaffolds using common 3D printing materials. 3D printed substrates were shown to support hPSC-CM attachment and the formation of uniform, contracting monolayers with high purity and viability. Successful attachment inside and retrieval of cells from the HDAS architecture also reveals the potential for 3D printed scaffolds to be applied in future large-scale 2D hPSC-CM manufacturing.