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Am J Physiol Cell Physiol 283: C1557-C1565, 2002. First published July 17, 2002; doi:10.1152/ajpcell.00595.2001
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Vol. 283, Issue 5, C1557-C1565, November 2002

Mechanical stimulation improves tissue-engineered human skeletal muscle

Courtney A. Powell1, Beth L. Smiley2, John Mills2, and Herman H. Vandenburgh1,2,3

1 Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island 02912; 2 Cell Based Delivery, Incorporated, Providence, Rhode Island 02906; and 3 Department of Pathology, Brown University Medical School/The Miriam Hospital, Providence, Rhode Island 02906

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

muscle hypertrophy; viscoelasticity; tension; collagen gel; force transducer; organogenesis


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