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News Dynamic model that tests engineered functional 3-D tissues to failure

Article in 'News' Written by Arul Prakash Published Dec 11, 2013

  1. Researchers have succeeded in developing a dynamic mathematics model for testing 3-D tissue structures under extreme conditions that could help design better tissues.

    Growth in tissue engineering has never been faster, so much so that the day is not far when a complete organ can be engineered for repair or transplant. Even though researchers already have techniques to grow and maintain these 3-D tissues they still needed a model to test the design of tissues.

    A team of researchers from Brown University and ETH Zurich led by Prof Vivek Shenoy from Brown University have developed a dynamic model of the stresses that stretch growing tissue.The study published in the Proceedings of The National Academy of Sciences revealed a series of experiments that were used to develop the model.

    Incidentally, it was also the first dynamic model that has considered the intrinsic and complicated feedback effects of cells through molecular motors, that could create a tear in the tissue owing to external stresses from the environment.

    “An important theme in regenerative medicine is that tissues and cells can alter their properties and behaviors, such as whether or not they want to divide, based on biochemical cues as well as mechanical cues,” Shenoy said. “Our aim was to generate a more comprehensive understanding of some of those cues, so we can build more accurate models to predict how tissues will behave when we grow them in the lab.”

    Researchers showed particular interest in studying the pull movements in tissues and much of these movement were governed by myosin, a molecular motor that helps muscles contract.

    tissue-dogbone.
    When cells in developing tissue pull on each other in these dogbone-shaped wells, they first break in the long middle section.
    Heart tissue was used an sample in experiments with myosin as a control to understand its role in tissue stability. To force the tissues to stretch rather than contract researchers grew them special environments constructed with two ring shaped wells connected by a narrow bridge.

    “Over the course of 30 hours or so, the cells pull on one another until the middle of the bone breaks. A similar process happens in each of the rings afterwards as well,” Shenoy said. “You can’t really hold the tissue and have it stable in this shape. It will find a way to pull, due to the myosin in the cells, and this leads to a major morphological instability.”

    Researchers using mysoin inhibitors were able to prove its role in morphological instability as mysoin deactivation caused tissues not to break. Heart tissue was strung between two posts to test how strongly can the cells pull on heir environments. The measure of tissue's pull gave researchers a glimpse into another factor that affects myosin's activity.

    “In the control set-up with the amount of collagen you would normally see in the heart, we see this bridge of tissue pull itself apart by day three,” Shenoy said, ”If you increase the collagen, or make the posts less stiff, you see that the tissues becomes more stable.”

    ”The myosin in the cells are pulling on actin filaments attached to the inside of the cells’ membranes, but if you anchor the cells, the contraction rate will decrease, eventually going to zero. That’s isometric tension at work,” he said.

    “This model will be helpful in figuring out the kind of geometry to grow artificial tissues in, such that they will redistribute the stress from these factors so they are stable,” Shenoy said. “A honeycomb, for example, can be stable and have the advantage of having channels where you can diffuse nutrients to all the cells, like a circulatory system. Our model would help you figure out the ideal spacing and diameters for the holes.”

    This study not only gives insights into tissue engineering by allowing better prediction of transformation in undifferentiated cells but could also be used study to morphogenesis, a in stage embryonic development.

    Further reading: Necking and failure of constrained 3D microtissues induced by cellular tension
    Hailong Wanga, Alexander A. Svoronosb, Thomas Boudouc, Mahmut Selman Sakard, Jacquelyn Youssef Schellb, Jeffrey R. Morganb, Christopher S. Chenc, and Vivek B. Shenoya.
    • Arul Prakash

      Article by Arul Prakash

      Editor and founder of BiotechCareer.Org. He is an Industrial Biotechnologists and also a web developer, gooner, blogger, and foodie.

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