Direct 3D bioprinting of cardiac micro-tissues mimicking native myocardium.

作者: Justin Liu , Kathleen Miller , Xuanyi Ma , Sukriti Dewan , Natalie Lawrence

DOI: 10.1016/J.BIOMATERIALS.2020.120204

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摘要: Abstract The heart possesses a complex three-dimensional (3D) laminar myofiber organization; however, because engineering physiologically relevant 3D tissues remains technical challenge, the effects of cardiomyocyte alignment on excitation-contraction coupling, shortening and force development have not been systematically studied. Cellular shape orientations in can be controlled by scaffold microstructures encapsulating cells near these geometric cues. Here, we show that novel method cell encapsulation methacrylated gelatin (GelMA) scaffolds patterned via Microscale Continuous Optical Printing (μCOP) rapidly micropattern neonatal mouse ventricular cardiomyocytes (NMVCMs) photocrosslinkable hydrogels. Encapsulated preferentially align with engineered microarchitecture display morphology myofibril phenotypic myocardium vivo. Utilizing μCOP system, an asymmetric, multi-material, cantilever-based was directly printed, so produced microtissue transmitted onto single deformable pillar. Aligned encapsulated NMVCM nearly 2 times compared to aligned 2D seeded samples. To further highlight flexibility μCOP, NMVCMs were several patterns compare varying degrees tissue displacement synchronicity. Well cultured generated 4–10 contractile less anisotropically constructs. Finally, normalized fluo-4 fluorescence NMVCM-encapsulated structures showed characteristic calcium transient waveforms increased magnitude rate decline during treatment 100 nM isoproterenol. This instrumented cardiac serves as vitro model system great potential for use disease modeling drug screening.

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