HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 98/2/706    most recent 00273.2004v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Huang, Y.-C. Articles by Baar, K. Search for Related Content PubMed PubMed Citation Articles by Huang, Y.-C. Articles by Baar, K.

INNOVATIVE METHODOLOGY

Rapid formation of functional muscle in vitro using fibrin gels

Departments of ¹Biomedical Engineering and ²Mechanical Engineering, ³Institute of Gerontology, University of Michigan, Ann Arbor, Michigan; and ⁴Harvard-Massachusetts Institute of Technology Health Sciences and Technology, Cambridge, Massachusetts

Submitted 12 March 2004 ; accepted in final form 4 September 2004

The transition of a muscle cell from a differentiated myotube into an adult myofiber is largely unstudied. This is primarily due to the difficulty of isolating specific developmental stimuli in vivo and the inability to maintain viable myotubes in culture for sufficient lengths of time. To address these limitations, a novel method for rapidly generating three-dimensional engineered muscles using fibrin gel casting has been developed. Myoblasts were seeded and differentiated on top of a fibrin gel. Cell-mediated contraction of the gel around artificial anchors placed 12 mm apart culminates 10 days after plating in a tubular structure of small myotubes (10-µm diameter) surrounded by a fibrin gel matrix. These tissues can be connected to a force transducer and electrically stimulated between parallel platinum electrodes to monitor physiological function. Three weeks after plating, the three-dimensional engineered muscle generated a maximum twitch force of 329 ± 26.3 µN and a maximal tetanic force of 805.8 ± 55 µN. The engineered muscles demonstrated normal physiological function including length-tension and force-frequency relationships. Treatment with IGF-I resulted in a 50% increase in force production, demonstrating that these muscles responded to hormonal interventions. Although the force production was maximal at 3 wk, constructs can be maintained in culture for up to 6 wk with no intervention. We conclude that fibrin-based gels provide a novel method to engineer three-dimensional functional muscle tissue and that these tissues may be used to model the development of skeletal muscle in vitro.

three dimensional; tissue engineering; developmental biology

This article has been cited by other articles:

				British Orthodontic Society, UTG session abstracts J. Orthod., March 1, 2008; 35(1): 52 - 56. [Full Text] [PDF]

				Y.-C. Huang, R. G. Dennis, and K. Baar Cultured slow vs. fast skeletal muscle cells differ in physiology and responsiveness to stimulation Am J Physiol Cell Physiol, July 1, 2006; 291(1): C11 - C17. [Abstract] [Full Text] [PDF]

				K. Baar New dimensions in tissue engineering: possible models for human physiology Exp Physiol, November 1, 2005; 90(6): 799 - 806. [Abstract] [Full Text] [PDF]

				L. Hecker, K. Baar, R. G. Dennis, and K. N. Bitar Development of a three-dimensional physiological model of the internal anal sphincter bioengineered in vitro from isolated smooth muscle cells Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G188 - G196. [Abstract] [Full Text] [PDF]