Effects of mechanical stimulation induced by compression and medium perfusion on cardiac tissue engineering

Michal Shachar, Nessi Benishti, Smadar Cohen

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Cardiac tissue engineering presents a challenge due to the complexity of the muscle tissue and the need for multiple signals to induce tissue regeneration in vitro. We investigated the effects of compression (1 Hz, 15% strain) combined with fluid shear stress (10-2-10-1 dynes/cm2) provided by medium perfusion on the outcome of cardiac tissue engineering. Neonatal rat cardiac cells were seeded in Arginine-Glycine-Aspartate (RGD)-attached alginate scaffolds, and the constructs were cultivated in a compression bioreactor. A daily, short-term (30 min) compression (i.e., "intermittent compression") for 4 days induced the formation of cardiac tissue with typical striation, while in the continuously compressed constructs (i.e., "continuous compression"), the cells remained spherical. By Western blot, on day 4 the expression of the gap junction protein connexin 43 was significantly greater in the "intermittent compression" constructs and the cardiomyocyte markers (α-actinin and N-cadherin) showed a trend of better preservation compared to the noncompressed constructs. This regime of compression had no effect on the proliferation of nonmyocyte cells, which maintained low expression level of proliferating cell nuclear antigen. Elevated secretion levels of basic fibroblast growth factor and transforming growth factor-β in the daily, intermittently compressed constructs likely attributed to tissue formation. Our study thus establishes the formation of an improved cardiac tissue in vitro, when induced by combined mechanical signals of compression and fluid shear stress provided by perfusion.

Original languageEnglish
Pages (from-to)1551-1559
Number of pages9
JournalBiotechnology Progress
Volume28
Issue number6
DOIs
StatePublished - 1 Nov 2012

Keywords

  • Bioreactor
  • Cardiac tissue engineering
  • Compression
  • Perfusion
  • RGD-alginate scaffold
  • Stimulation

ASJC Scopus subject areas

  • Biotechnology

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