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

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

Author information

1
Biomedical Microsystems Development Group, Charles Stark Draper Laboratory, Cambridge, MA 02139-4307, United States.
2
Harvard-MIT Division of Health Sciences and Technology, David H. Koch Institute for Integrative Cancer Research, and Institute of Medical Engineering and Science, MIT, Cambridge, MA, United States.
3
Department of Biomedical Engineering, Columbia University, New York, NY, United States.
4
Biomedical Microsystems Development Group, Charles Stark Draper Laboratory, Cambridge, MA 02139-4307, United States; Harvard-MIT Division of Health Sciences and Technology, David H. Koch Institute for Integrative Cancer Research, and Institute of Medical Engineering and Science, MIT, Cambridge, MA, United States. Electronic address: lfreed@draper.com.

Abstract

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)

PMID:
24240126
PMCID:
PMC3946629
DOI:
10.1016/j.yexcr.2013.11.005
[Indexed for MEDLINE]
Free PMC Article

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