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Automated fabrication of a scalable heart-on-a-chip device by 3D printing of thermoplastic elastomer nanocomposite and hot embossing

引用

Bioactive Materials 2024年第3期33卷 46-60页

作者： Qinghua Wu Ruikang Xue Yimu Zhao Kaitlyn Ramsay Erika Yan Wang houman savoji Teodor Veres Sarah H.Cartmell Milica Radisic Institute of Biomedical Engineering University of TorontoTorontoOntarioM5S 3G9Canada Toronto General Research Institute University Health NetworkTorontoOntarioM5G 2C4Canada Department of Materials School of Natural SciencesFaculty of Science and Engineering and The Henry Royce InstituteRoyce Hub BuildingThe University of ManchesterManchesterUK Koch Institute for Integrative Cancer Research Massachusetts Institute of TechnologyCambridgeMA02139USA Department of Chemical Engineering and Applied Chemistry University of TorontoTorontoOntarioM5S 3E5Canada Institute of Biomedical Engineering and Department of Pharmacology and Physiology University of MontrealMontrealQuebecH3T 1J4Canada Research Center Centre Hospitalier Universitaire Sainte-JustineMontrealQuebecH3T 1C5Canada Montreal TransMedTech Institute MontrealQuebecH3T 1J4Canada National Research Council of Canada BouchervilleQCJ4B 6Y4Canada Department of Mechanical and Industrial Engineering University of TorontoTorontoOntarioM5S 3G8Canada Terrence Donnelly Centre for Cellular&Biomolecular Research University of TorontoTorontoONM5S 3E1Canada

The successful translation of organ-on-a-chip devices requires the development of an automated workflow for device fabrication, which is challenged by the need for precise deposition of multiple classes of materials in micro-meter scaled configurations. Many current heart-on-a-chip devices are produced manually, requiring the expertise and dexterity of skilled operators. Here, we devised an automated and scalable fabrication method to engineer a Biowire II multiwell platform to generate human iPSC-derived cardiac tissues. This high-throughput heart-on-a-chip platform incorporated fluorescent nanocomposite microwires as force sensors, produced from quantum dots and thermoplastic elastomer, and 3D printed on top of a polystyrene tissue culture base patterned by hot embossing. An array of built-in carbon electrodes was embedded in a single step into the base, flanking the microwells on both sides. The facile and rapid 3D printing approach efficiently and seamlessly scaled up the Biowire II system from an 8-well chip to a 24-well and a 96-well format, resulting in an increase of platform fabrication efficiency by 17,5000-69,000% per well. The device’s compatibility with long-term electrical stimulation in each well facilitated the targeted generation of mature human iPSC-derived cardiac tissues, evident through a positive force-frequency relationship, post-rest potentiation, and well-aligned sarcomeric apparatus. This system’s ease of use and its capacity to gauge drug responses in matured cardiac tissue make it a powerful and reliable platform for rapid preclinical drug screening and development.

关键词： Heart-on-a-chip Additive manufacturing Electrical stimulation Cardiomyocyte Drug testing

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