Biomimetic scaffold combined with electrical stimulation and growth factor promotes tissue engineered cardiac development.
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.
Biomedical Microsystems Development Group, Charles Stark Draper Laboratory, Cambridge, MA 02139-4307, United States.
Hyoungshin
H
Park
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.
Benjamin L
BL
Larson
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.
Martin E
ME
Kolewe
Department of Biomedical Engineering, Columbia University, New York, NY, United States.
Gordana
G
Vunjak-Novakovic
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.
Lisa E
LE
Freed
D000818:Animals; D000831:Animals, Newborn; D001696:Biomechanical Phenomena; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D006321:Heart / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D055616:Microtechnology; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
D036341:Intercellular Signaling Peptides and Proteins
Anisotropy; Electrical stimulation; Heart; Insulin-like growth factor-1; Poly(glycerol sebacate)