Next-generation engineered heart tissue platform that enables precise tuning of mechanical properties of microenvironment to study the structure, development, and function of cultured cells or human-derived cardiac tissues.
Engineering heart tissue (EHT) platforms have the potential to study heart physiology, disease pathology, and therapeutic efficacy. Although many existing platforms are able to model basic aspects of the human heart, few offer tunable control of key biomechanical parameters and long-term culture under physiologically appropriate mechanical conditions.
The
investigators developed a versatile, user-friendly EHT fabrication and cell culture system that allows for control over mechanical forces during tissue formation, maintenance, testing, and imaging. The platform enables investigators to fabricate tissues under isometric conditions, culture EHT’s long-term under auxotonic conditions, image the tissues, reproducibly adjust preload/afterload conditions, transfer the tissues to mechanical testing devices, and maintain sterility throughout.
The invention features a movable casting well that locks in the tissue and prevents its shortening, as well as adapts between two key modes that affect tissue longevity and contraction properties – isometric and auxotonic. Second, the platform contains a molded mounting string and custom displacement pins that allow for reversible and reproducible control of tissue length (preload) and resistance to shortening (afterload). Third, the platform allows for intact tissue transfer to external devices for rigorous mechanical testing. Finally, the system in its entirety is fitted to a standard well format, allowing for simple adaptation by users across applications. The precision of this platform permits sustained culture of living myocardial slices from human hearts or animal models, offering the same versatile attributes of tunable preload and afterload, sterile imaging during culture, and intact tissue transfer for rigorous mechanical testing across studies.