Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture

Adam W. Feinberg, Patrick W. Alford, Hongwei Jin, Crystal M Ripplinger, Andreas A. Werdich, Sean P. Sheehy, Anna Grosberg, Kevin Kit Parker

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

The heart is a muscular organ with a wrapping, laminar structure embedded with neural and vascular networks, collagen fibrils, fibroblasts, and cardiac myocytes that facilitate contraction. We hypothesized that these non-muscle components may have functional benefit, serving as important structural alignment cues in inter- and intra-cellular organization of cardiac myocytes. Previous studies have demonstrated that alignment of engineered myocardium enhances calcium handling, but how this impacts actual force generation remains unclear. Quantitative assays are needed to determine the effect of alignment on contractile function and muscle physiology. To test this, micropatterned surfaces were used to build 2-dimensional myocardium from neonatal rat ventricular myocytes with distinct architectures: confluent isotropic (serving as the unaligned control), confluent anisotropic, and 20 μm spaced, parallel arrays of multicellular myocardial fibers. We combined image analysis of sarcomere orientation with muscular thin film contractile force assays in order to calculate the peak sarcomere-generated stress as a function of tissue architecture. Here we report that increasing peak systolic stress in engineered cardiac tissues corresponds with increasing sarcomere alignment. This change is larger than would be anticipated from enhanced calcium handling and increased uniaxial alignment alone. These results suggest that boundary conditions (heterogeneities) encoded in the extracellular space can regulate muscle tissue function, and that structural organization and cytoskeletal alignment are critically important for maximizing peak force generation.

Original languageEnglish (US)
Pages (from-to)5732-5741
Number of pages10
JournalBiomaterials
Volume33
Issue number23
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Cardiac tissue engineering
  • Cardiomyocyte
  • Fibronectin
  • Micropatterning
  • Polydimethylsiloxane

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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  • Cite this

    Feinberg, A. W., Alford, P. W., Jin, H., Ripplinger, C. M., Werdich, A. A., Sheehy, S. P., Grosberg, A., & Parker, K. K. (2012). Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture. Biomaterials, 33(23), 5732-5741. https://doi.org/10.1016/j.biomaterials.2012.04.043