Abstract
The development of in vitro methods of engineering three-dimensional cardiac tissues can be useful for tissue replacement, diagnostics and drug discovery. Here, we introduce the use of patterned hyaluronic acid (HA) substrates generated using microfluidic patterning as a method of fabricating 3D cardiac organoids. HA micropatterns served as inductive templates for organoid assembly. Upon seeding, cardiomyocytes elongated and aligned along the pattern direction attaching preferentially to the glass substrate and the interface between HA patterns and glass substrate. After 3 days in culture, the linearly aligned myocytes detached from the surface and formed contractile cardiac organoids. The procedure can be utilized to simply, rapidly and inexpensively create in vitro cardiac tissue models.
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Acknowledgments
The authors would like to thank Lorain Chiu for immunostaining and Draper Laboratories for microfabrication. This work was supported by grants from Ontario Research and Development Challenge Fund (ORDCF), National Science and Engineering Research Council (NSERC) and Canada Foundation for Innivation (CF)) (MR) National Institutes of Health (NIH) Grant No P41 EB002520–01A1 (Tissue Engineering Resource Center, GV) R01HL076485 (GV) and NIH grants No HL060435, DE13023 and DE16516 (RL).
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Author’s contributions: AK, RL, GV and MR designed experiments and conceived the ideas. AK, MR, GE, JY performed experiments. AK, GE and JY fabricated and analyzed the patterned substrates. SK and MR analyzed the cardiomyocyte data. All authors read and approved the final manuscript.
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Khademhosseini, A., Eng, G., Yeh, J. et al. Microfluidic patterning for fabrication of contractile cardiac organoids. Biomed Microdevices 9, 149–157 (2007). https://doi.org/10.1007/s10544-006-9013-7
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DOI: https://doi.org/10.1007/s10544-006-9013-7