Biomimetic scaffold combined with electrical stimulation and growth factor promotes tissue engineered cardiac development

Exp Cell Res. 2014 Feb 15;321(2):297-306. doi: 10.1016/j.yexcr.2013.11.005. Epub 2013 Nov 14.


Toward developing biologically sound models for the study of heart regeneration and disease, we cultured heart cells on a biodegradable, microfabricated poly(glycerol sebacate) (PGS) scaffold designed with micro-structural features and anisotropic mechanical properties to promote cardiac-like tissue architecture. Using this biomimetic system, we studied individual and combined effects of supplemental insulin-like growth factor-1 (IGF-1) and electrical stimulation (ES). On culture day 8, all tissue constructs could be paced and expressed the cardiac protein troponin-T. IGF-1 reduced apoptosis, promoted cell-to-cell connectivity, and lowered excitation threshold, an index of electrophysiological activity. ES promoted formation of tissue-like bundles oriented in parallel to the electrical field and a more than ten-fold increase in matrix metalloprotease-2 (MMP-2) gene expression. The combination of IGF-1 and ES increased 2D projection length, an index of overall contraction strength, and enhanced expression of the gap junction protein connexin-43 and sarcomere development. This culture environment, designed to combine cardiac-like scaffold architecture and biomechanics with molecular and biophysical signals, enabled functional assembly of engineered heart muscle from dissociated cells and could serve as a template for future studies on the hierarchy of various signaling domains relative to cardiac tissue development.

Keywords: Anisotropy; Electrical stimulation; Heart; Insulin-like growth factor-1; Poly(glycerol sebacate).

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomechanical Phenomena
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Cells, Cultured
  • Electric Stimulation / methods
  • Heart* / drug effects
  • Heart* / physiology
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Microtechnology
  • Myocardium / cytology*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering / instrumentation
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*


  • Intercellular Signaling Peptides and Proteins