Dynamic Control of Contractile Force in Engineered Heart Tissue
Dynamic Control of Contractile Force in Engineered Heart Tissue
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DOI：
10.1109/tbme.2023.3239594
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发表时间：
2023-07-01
影响因子：
4.6
通讯作者：
Bifano, Thomas G.
中科院分区：
文献类型：
--
作者：
Li, Huate;Sundaram, Subramanian;Bifano, Thomas G.
Three-dimensional engineered heart tissues (EHTs) derived from human induced pluripotent stem cells (iPSCs) have become an important resource for both drug toxicity screening and research on heart disease. A key metric of EHT phenotype is the contractile (twitch) force with which the tissue spontaneously beats. It is well-known that cardiac muscle contractility - its ability to do mechanical work - depends on tissue prestrain (preload) and external resistance (afterload). Objectives: Here, we demonstrate a technique to control afterload while monitoring contractile force exerted by EHTs. Methods: We developed an apparatus that can regulate EHT boundary conditions using real-time feedback control. The system is comprised of a pair of piezoelectric actuators that can strain the scaffold and a microscope that can measure EHT force and length. Closed loop control allows dynamic regulation of effective EHT boundary stiffness. Results: When controlled to switch instantaneously from auxotonic to isometric boundary conditions, EHT twitch force immediately doubled. Changes in EHT twitch force as a function of effective boundary stiffness were characterized and compared to twitch force in auxotonic conditions. Conclusion: EHT contractility can be regulated dynamically through feedback control of effective boundary stiffness. Significance: The capacity to alter the mechanical boundary conditions of an engineered tissue dynamically offers a new way to probe tissue mechanics. This could be used to mimic afterload changes that occur naturally in disease, or to improve mechanical techniques for EHT maturation.
