Micro-Topography Enhances Directional Myogenic Differentiation of Skeletal Precursor Cells
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1052-DD03-27
Micro-Topography Enhances Directional Myogenic Differentiation of Skeletal Precursor Cells Yi Zhao Department of Biomedical Engineering, The Ohio State University, 294 Bevis Hall, 1080 Carmack Road, Columbus, OH, 43210 ABSTRACT Skeletal muscle tissues were constructed by differentiating in vitro cultured skeletal myoblasts using an array of closely spaced linear microstructures. The adaptation of skeletal myoblasts has been characterized with immunoflurescence microscopy during cell proliferation and differentiation. In particular, the dependence of the alignment efficiency on the dimensions of the microstructures was studied. The morphology difference of the myotubes in the threedimensional tissues was reported. This paper holds the promise of efficient on-chip fabrication of skeletal muscle tissues and has an important implication in direct muscle repair and muscular mechanics. INTRODUCTION Skeletal muscle accounts for 48% of the human body weight and is the major consumer of body fuels [1], largely responsible for the voluntary control and active movement. The prototypic skeletal muscle is composed of striated myotubes that are arrayed in parallel with one another along a common axis. Each multinucleated myotube functions as a single cell and spans the entire length of the muscle. Such striated organization is essential for generation of contractile forces sufficient for body movement at the expense of ATP consumption. In cases of inherited muscular dystrophies, accidents, or removal of tumor tissues, the striated structures of the skeletal muscles are damaged to certain extents, which directly affect the physiological and contractile performance of the muscles. There has been a long-standing research interest to develop striate muscle implants that mimic the architectural organization and physiological function of intact muscles for the repair and replacement against muscular abnormities [2-4]. Particularly, the skeletal precursor cell is a relatively accessible cell source with myogenic potential, and can be directed into musculoskeletal tissues. Therefore, skeletal myoblasts transplantation has been developed as an attempt to substitute the segments of the damaged muscles against muscular abnormities [2, 3]. In this practice, muscles with highly organized structures and aligned myotubes are preferred as they mimic the natural muscular morphology. This is expected to help the fusion between the implanted tissues with the reception regions, and to enhance the physiological functions. To this end, a variety of engineering approaches have been developed to regulate the alignment of skeletal myotubes, including the use of aligned collagen gel system [5], microcontact printing of cell-adhesive domains [6], and cyclic mechanical loadings [7]. In particular, topographic modulation is an effective method for regulating cell growth and
proliferation. Various studies have indicated that it is possible to align the skeletal myoblasts and myotubes using micro-scale topographies, such as nano fibers [8], mic
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