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      Micro Vacuum Chuck and Tensile Test System for Bio-Mechanical Evaluation of 3D Tissue Constructed of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPS-CM)

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          Abstract

          In this report, we propose a micro vacuum chuck (MVC) which can connect three-dimensional (3D) tissues to a tensile test system by vacuum pressure. Because the MVC fixes the 3D tissue by vacuum pressure generated on multiple vacuum holes, it is expected that the MVC can fix 3D tissue to the system easily and mitigate the damage which can happen by handling during fixing. In order to decide optimum conditions for the size of the vacuum holes and the vacuum pressure, various sized vacuum holes and vacuum pressures were applied to a normal human cardiac fibroblast 3D tissue. From the results, we confirmed that a square shape with 100 µm sides was better for fixing the 3D tissue. Then we mounted our developed MVCs on a specially developed tensile test system and measured the bio-mechanical property (beating force) of cardiac 3D tissue which was constructed of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM); the 3D tissue had been assembled by the layer-by-layer (LbL) method. We measured the beating force of the cardiac 3D tissue and confirmed the measured force followed the Frank-Starling relationship. This indicates that the beating property of cardiac 3D tissue obtained by the LbL method was close to that of native cardiac tissue.

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          Capturing complex 3D tissue physiology in vitro.

          The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.
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            Three-dimensionally printed biological machines powered by skeletal muscle.

            Combining biological components, such as cells and tissues, with soft robotics can enable the fabrication of biological machines with the ability to sense, process signals, and produce force. An intuitive demonstration of a biological machine is one that can produce motion in response to controllable external signaling. Whereas cardiac cell-driven biological actuators have been demonstrated, the requirements of these machines to respond to stimuli and exhibit controlled movement merit the use of skeletal muscle, the primary generator of actuation in animals, as a contractile power source. Here, we report the development of 3D printed hydrogel "bio-bots" with an asymmetric physical design and powered by the actuation of an engineered mammalian skeletal muscle strip to result in net locomotion of the bio-bot. Geometric design and material properties of the hydrogel bio-bots were optimized using stereolithographic 3D printing, and the effect of collagen I and fibrin extracellular matrix proteins and insulin-like growth factor 1 on the force production of engineered skeletal muscle was characterized. Electrical stimulation triggered contraction of cells in the muscle strip and net locomotion of the bio-bot with a maximum velocity of ∼ 156 μm s(-1), which is over 1.5 body lengths per min. Modeling and simulation were used to understand both the effect of different design parameters on the bio-bot and the mechanism of motion. This demonstration advances the goal of realizing forward-engineered integrated cellular machines and systems, which can have a myriad array of applications in drug screening, programmable tissue engineering, drug delivery, and biomimetic machine design.
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              Bioprinting for cancer research.

              Bioprinting offers the ability to create highly complex 3D architectures with living cells. This cutting-edge technique has significantly gained popularity and applicability in several fields. Bioprinting methods have been developed to effectively and rapidly pattern living cells, biological macromolecules, and biomaterials. These technologies hold great potential for applications in cancer research. Bioprinted cancer models represent a significant improvement over previous 2D models by mimicking 3D complexity and facilitating physiologically relevant cell-cell and cell-matrix interactions. Here we review bioprinting methods based on inkjet, microextrusion, and laser technologies and compare 3D cancer models with 2D cancer models. We discuss bioprinted models that mimic the tumor microenvironment, providing a platform for deeper understanding of cancer pathology, anticancer drug screening, and cancer treatment development.
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                Author and article information

                Journal
                Micromachines (Basel)
                Micromachines (Basel)
                micromachines
                Micromachines
                MDPI
                2072-666X
                19 July 2019
                July 2019
                : 10
                : 7
                : 487
                Affiliations
                [1 ]Department of Mechanical Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan
                [2 ]Global Center for Medical Engineering and Informatics, Osaka University, 2-1 Yamada-oka Suita, Osaka 565-0871, Japan
                [3 ]Building Block Science Joint Research Chair, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan
                [4 ]Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
                Author notes
                [* ]Correspondence: morishima@ 123456mech.eng.osaka-u.ac.jp ; Tel.: +81-6-6879-7343
                Article
                micromachines-10-00487
                10.3390/mi10070487
                6680730
                31331014
                53848772-ec0c-400b-8481-08ea4163f104
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 June 2019
                : 17 July 2019
                Categories
                Article

                beating force,bio-mechanical property,cardiac 3d tissue,human induced pluripotent stem cell-derived cardiomyocytes (hips-cm),tissue engineering,vacuum chuck

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