4.1 Article

Muscle on a chip: In vitro contractility assays for smooth and striated muscle

Journal

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.vascn.2012.04.001

Keywords

Assay; Contractility; In vitro; Micropatterning; Muscular micro-devices; Tissue engineering

Funding

  1. Nanoscale Science and Engineering Center of the National Science Foundation [PHY-0117795]
  2. Harvard Materials Research Science and Engineering Center under NSF [DMR-0213805]
  3. Harvard Stem Cell Institute
  4. GlaxoSmithKline
  5. NIH/NINDS [1 U01 NS073474-01]
  6. NIH-NHBLI [1 R01 HL079126]
  7. Direct For Mathematical & Physical Scien
  8. Division Of Materials Research [820484] Funding Source: National Science Foundation

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Introduction: To evaluate the viability of a muscle tissue, it is essential to measure the tissue's contractile performance as well as to control its structure. Accurate contractility data can aid in development of more effective and safer drugs. This can be accomplished with a robust in vitro contractility assay applicable to various types of muscle tissue. Methods: The devices developed in this work were based on the muscular thin film (MTF) technology, in which an elastic film is manufactured with a 2D engineered muscle tissue on one side. The tissue template is made by patterning extracellular matrix with microcontact printing. When muscle cells are seeded on the film, they self-organize with respect to the geometric cues in the matrix to form a tissue. Results: Several assays based on the MTF on a chip technology are demonstrated. One such assay incorporates the contractility assay with striated muscle into a fluidic channel. Another assay platform incorporates the MTFs in a multi-well plate, which is compatible with automated data collection and analysis. Finally, we demonstrate the possibility of analyzing contractility of both striated and smooth muscle simultaneously on the same chip. Discussion: In this work, we assembled an ensemble of contractility assays for striated and smooth muscle based on muscular thin films. Our results suggest an improvement over current methods and an alternative to isolated tissue preparations. Our technology is amenable to both primary harvests cells and cell lines, as well as both human and animal tissues. (C) 2012 Elsevier Inc. All rights reserved.

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