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Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol–gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties.more » « less
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Lee, Keel Yong; Park, Sung-Jin; Matthews, David G.; Kim, Sean L.; Marquez, Carlos Antonio; Zimmerman, John F.; Ardoña, Herdeline Ann; Kleber, Andre G.; Lauder, George V.; Parker, Kevin Kit (, Science)Integration of mechanoelectrical signaling and cardiac automaticity enables an autonomously swimming biohybrid fish analog.more » « less
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Chang, Huibin; Liu, Qihan; Zimmerman, John F.; Lee, Keel Yong; Jin, Qianru; Peters, Michael M.; Rosnach, Michael; Choi, Suji; Kim, Sean L.; Ardoña, Herdeline Ann; et al (, Science)Helical alignments within the heart’s musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart’s musculature using current techniques. Here we report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.more » « less
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