Objective: To develop a bioink capable of promoting hiPSC proliferation and cardiomyocyte differentiation in order to 3D print electromechanically functional, chambered organoids composed of contiguous cardiac muscle.
Methods and Results: We optimized a photo-crosslinkable formulation of native extracellular matrix (ECM) proteins and used this bioink to 3D print hiPSC-laden structures with two chambers and a vessel inlet and outlet. After hiPSCs proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump (hChaMP). hChaMPs demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease.
Conclusions: This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a testbed for cardiac medical devices and eventually lead to therapeutic tissue grafting.
- biocompatible materials
- extracellular matrix proteins
- induced pluripotent stem cells
- myocytes, cardiac
- tissue engineering
PubMed: MeSH publication types
- Journal Article