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Am J Physiol Cell Physiol (July 17, 2002). doi:10.1152/ajpcell.00595.2001
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Articles in PresS, published online ahead of print July 17, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00595.2001
Submitted on December 20, 2001
Accepted on June 17, 2002

Mechanical Stimulation Improves Tissue Engineered Human Skeletal Muscle

Courtney A. Powell1, Beth L. Smiley2, John Mills2, and Herman H. Vandenburgh3*

1 Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, USA
2 Cell Based Delivery, Inc., Providence, RI, USA
3 Cell Based Delivery, Inc., Providence, RI, USA; Pathology, Miriam Hospital, Providence, RI, USA; Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, USA

* To whom correspondence should be addressed. E-mail: herman_vandenburgh{at}brown.edu.

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGELTM, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for eight to sixteen 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 significantly increased the HBAM elasticity 2-3 fold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogues as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.




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