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Biomanufacturing

Biomaterials/3D Printing

Engineered 3D In Vitro Ventricle Models with Fiber Infused Gel Ink Printing

Thursday, October 12, 2023
9:10 AM – 9:20 AM PDT
Location: 333 (Center, Level 3)
Introduction:: Extracellular matrix (ECM) acts as topological and biochemical cues for the cells to support structural and functional tissue development. In the heart, this is also important to form hierarchically organized muscle tissues which are essential for cardiac excitation-contraction coupling, resulting in the cyclic heart beating. In an effort to build an engineered model of the heart in vitro, researchers have developed ECM-based biopolymer materials or engineering techniques such as microcontact printing, photolithography, fiber spinning, and 3D printing. Particularly, 3D printing has been increasingly utilized due to its facile design, editing capabilities, and its ability to construct intricate 3D organ shapes. However, significant challenges still need to be overcome to control tissue self-organization and 3D geometric shape simultaneously due to the lack of microstructural features to promote cellular alignment.


Materials and Methods:: We developed our 3D printable inks by infusing gelatin fibers into a gelatin and alginate hydrogel. We produced gelatin fibers using focused rotary jet spinning and truncated them at a length of 85.9 ± 2.53 µm with a diameter of 4.20 ± 0.23 µm. Incorporating gelatin fibers into the hydrogel modifies the ink viscosity and rheological properties. Specifically, when the fiber infused gel (FIG) ink was extruded through the nozzle during printing, it behaved as a liquid. After extrusion, the FIG ink behaved like an elastic gel. This sol-gel transition property allowed for the precise printing of free-standing 3D structures without additional supporting materials such as a left ventricle, dual ventricles, and a heart valve. In addition, shear-induced fiber alignment maintained 3D printed scaffolds, providing microscale geometric cues for cellular organization. As a result, FIG printed scaffolds potentiate intra- and inter-cellular organization of cardiomyocytes by demonstrating myofibrillar and nucleus organization.


Results, Conclusions, and Discussions:: The structurally recapitulated engineered cardiac tissue replicates the heart's spatiotemporal excitation and contraction dynamics in vitro. Cardiac tissues on FIG scaffolds exhibited anisotropic Ca2+ propagation as the rapid conduction was along the aligned direction. In addition, preferential electromechanical coupling of cardiomyocytes along the printing orientation resulted in pattern-specific cyclic deformation in response to electrical stimulation. We cultured human induced pluripotent stem cell cardiomyocytes (hiPSC-CM) on a 3D printed ventricle scaffold, building an in vitro engineered ventricle model with anisotropic cardiac tissue along the printing direction. To evaluate the contractility of hiPSC-CM ventricle models, we measured flow movement at the basal opening and calculated the ventricle models' volumetric changes using particle imaging velocimetry. As a result, the volumetric change during the cardiac cycle was 5.94 ± 1.66 % (n = 4, mean ± SEM), 8~20 times higher than previously reported ejection fraction from hiPSC-CM in vitro ventricle models. This work suggests that FIG ink printing will play an essential role in advancing the 3D bioprinting processes to recapitulate the structure and function of the heart at both the cellular scale and the microscopic organ level.


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