Speaker
Description
Cardiovascular diseases (CVDs) remain the leading cause of death globally, with myocardial infarction (MI) as a major contributor. Traditional 2D cultures and animal models fail to recapitulate the native electromechanical properties and pathological responses of the human myocardium. Recent advancements in human-induced pluripotent stem cell (hiPSC) technology and 3D bioprinting have enabled the fabrication of structurally and functionally relevant cardiac tissues that can closely mimic the native myocardium. However, existing platforms still lack robust, real-time monitoring of electrophysiology of cardiac tissue, particularly for simultaneously measuring both contractile force and field potential in 3D cardiac tissues.
In this study, we developed a 3D origami biosensor-integrated platform for simultaneously real time monitoring of 3D bioprinted cardiac tissue contraction force and field potential, enhancing the fidelity and accuracy of the disease model and therapeutic screening. The 3D biosensor system was developed using polydimethylsiloxane (PDMS) as the substrate. Gold strain sensors and a microelectrode array (MEA) were patterned via photolithography and assembled using anisotropic conductive film (ACF) bonding. This multilayer sensor structure allows simultaneous mechanical and electrical signal acquisition. Cardiac tissue was engineered by co-culturing human-induced pluripotent cardiomyocytes (hiPSC-CMs) and Primary cardiac fibroblast (CFs) mixed in a heart-decellularized extracellular matrix (hdECM) hydrogel. The hydrogel was bioprinted and cultured directly on the biosensor. The integrated biosensor system successfully captured real-time contraction profiles and field potential signals from the 3D bioprinted cardiac constructs.
The integrated system can successfully capture high-resolution, real-time data on both mechanical contraction and field potential propagation, with minimal signal interference. Immunofluorescence staining performed on day 14 confirmed tissue maturation, with uniform expression of α-sarcomeric actinin (α-SA) and vimentin. The bioprinted constructs exhibited synchronous beating and stable, functional outputs over time. To mimic native myocardial ischemia, we created a hypoxic environment within the matured cardiac tissue by establishing an oxygen gradient using a gas-permeable barrier, replicating infarct and border zones of the post-MI state. The biosensor detected increased spontaneous beating, reduced contractility, and slowed conduction—hallmarks of electromechanical dysfunction. Treatment with the ARB losartan improved both beating rate and contractile amplitude, demonstrating the platform's capability for real-time drug response assessment.
In conclusion, we develop a next-generation MI-on-a-chip model that integrates 3D bioprinting with a soft, flexible biosensor platform for real-time monitoring of cardiac tissue's contractility and electrophysiological activity. This platform presents a platform bridges 3D bioprinting and sensor technology, enabling continuous, non-invasive tissue maturation and function monitoring. This integrated 3D biosensor is expected to enhance the fidelity of in vitro models and provide more accurate and comprehensive data on tissue responses, thereby advancing cardiac research and therapeutic development.
Acknowledgement: This work was supported by the Korea government programs as follows: the Ministry of Science and ICT (MSIT) under Grant No. [2020R1A5A8018367], [RS-2022-NR067329], and [RS-2024-00423107], the Ministry of Trade, Industry & Energy (MOTIE) under Grant No. [20012378], and the Ministry of Agriculture, Food and Rural Affairs (MAFRA) under Grant No. [RS-2024-00397026].
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