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Development of Myocardial Constructs Using Modulus-Matched Acrylated Polypropylene Glycol Triol (aPPGT) Substrate and Different Non-Myocyte Cell Populations.
MedLine Citation:
PMID:  21542698     Owner:  NLM     Status:  Publisher    
Tissue engineering approaches are currently being investigated for the restoration of myocardial function in heart failure patients, most commonly by combining cells with a substrate to form myocardial-like constructs. The final properties of these constructs are dependant on the characteristics of both the substrate and the cells used for fabrication. In order to create a construct with the appropriate mechanical properties required for any future therapeutic, we tailored an acrylated polypropylene glycol triol (aPPGT) substrate to the elastic modulus of heart tissue and then investigated the fabrication of myocardial-like constructs. We firstly assessed the aPPGT substrate alone in vivo, both under normal conditions and in an infarct model in mice, and found that there was a mild foreign body response with good integration of the substrate into the epicardial surface in mice hearts. We next studied the fabrication and properties of myocardial-like constructs by culturing mouse embryonic cardiomyocytes on the aPPGT substrate. In order to achieve myocardial-like concentrically contractile constructs, co-cultures with supportive stromal cells were found to be essential and both mouse heart derived stromal cells or bone-derived mouse mesenchymal stromal progenitor cells (mMSCs) could be used. These different stromal cell types produced myocardial-like constructs with different properties. The average beating rate of the constructs formed from mouse heart derived stromal cells was significantly higher those constructs formed using mMSCs. Conversely, the constructs formed using mMSCs had reduced fibrotic extracellular matrix secretion and increased hepatocyte growth factor expression. Both of these mMSC construct properties may enhance integration and therapeutic efficacy of the construct post implantation on the surface of the infarcted heart. This study thus demonstrates the formation of myocardial-like constructs using mechanically tailored aPPGT substrate and also demonstrates the effects of different stromal cell populations have on the properties of the resultant myocardial-like constructs, both of which are critical for future applications of tissue engineering in heart failure patients.
James E Hudson; Gary Brooke; Chris Blair; Ernst Wolvetang; Justin John Cooper-White
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-4
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  -     ISSN:  1937-335X     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Brisbane, Queensland, Australia;
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