CellBeat – CellBeat

Regenerative therapies require large quantities of functional cellular equivalents to restore or repair injured or diseased native tissues. For example, replenishment of the cardiomyocyte (CM) pool following heart failure requires ~ 109 cells. Synthetic materials in bioreactors provide unparalleled opportunities for large-scale CM manufacture in contrast to traditional Matrigel-based 2D culture. When derived from human induced pluripotent stem cells (hiPSCs), however, the functionality of the differentiated CMs is problematic for clinical application because they are fetal-like in character: hiPSC-CMs have proven to be rudimentary, showing poor contractility and risk of life-threatening arrhythmias. Thus, obtaining more mature hiPSC-derived CMs is of priority before safe implantation into cardiac patients. In 2D culture, active mechanical cues (e.g. stretch) have demonstrated the capacity to improve CM maturity. However, these protocols are challenging to use in bioreactor culture on microcarriers as the polymers are static. Herein, we aim to prepare the next generation of polymer microcarriers with nanostructured liquid crystalline segments for photoresponsive actuation. Microfluidic methods will be used to fabricate the nanostructured microcarriers with a bioactive layer for hiPSC-CMs expansion. Cell stretch protocols for maturation will be optimized in small scale bioreactors evaluating molecular, electrophysiological and functional CM readouts. These matured CMs will be evaluated in rodent and pig models of myocardial infarction, focusing on improving contractility and reducing arrhythmias in the large animal model. These beating nanostructured microcarriers will be a game changer for this technology and open uncharted territory for bioreactor cell manufacture by imposing active mechanical forces that can be broadly applied to any cell type responsive to this cue in vivo.