Automated fabrication of a scalable heart-on-a-chip device by 3D printing of thermoplastic elastomer nanocomposite and hot embossing.
Autor: | Wu Q; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9, Canada.; Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada., Xue R; Department of Materials, School of Natural Sciences, Faculty of Science and Engineering and The Henry Royce Institute, Royce Hub Building, The University of Manchester, Manchester, UK., Zhao Y; Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada., Ramsay K; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9, Canada., Wang EY; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Savoji H; Institute of Biomedical Engineering and Department of Pharmacology and Physiology, University of Montreal, Montreal, Quebec, H3T 1J4, Canada.; Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, H3T 1C5, Canada.; Montreal TransMedTech Institute, Montreal, Quebec, H3T 1J4, Canada., Veres T; National Research Council of Canada, Boucherville, QC, J4B 6Y4, Canada.; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, M5S 3G8, Canada., Cartmell SH; Department of Materials, School of Natural Sciences, Faculty of Science and Engineering and The Henry Royce Institute, Royce Hub Building, The University of Manchester, Manchester, UK., Radisic M; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9, Canada.; Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada.; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada.; Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada. |
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Jazyk: | angličtina |
Zdroj: | Bioactive materials [Bioact Mater] 2023 Nov 07; Vol. 33, pp. 46-60. Date of Electronic Publication: 2023 Nov 07 (Print Publication: 2024). |
DOI: | 10.1016/j.bioactmat.2023.10.019 |
Abstrakt: | 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. (© 2023 The Authors.) |
Databáze: | MEDLINE |
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