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Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations. Langmuir 2013 Sep 03;29(35):11109-17

Date

08/09/2013

Pubmed ID

23923967

Pubmed Central ID

PMC3838927

DOI

10.1021/la401702w

Scopus ID

2-s2.0-84883478950   63 Citations

Abstract

Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

Author List

Wang B, Wang G, To F, Butler JR, Claude A, McLaughlin RM, Williams LN, de Jongh Curry AL, Liao J

Author

Bo Wang PhD Assistant Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Actinin
Animals
Azacitidine
Biomarkers
Bioreactors
Cadherins
Cell Count
Cell Differentiation
Cell Survival
Cells, Cultured
Connexin 43
Electric Stimulation
Extracellular Matrix
Gene Expression
Humans
Mechanotransduction, Cellular
Myocytes, Cardiac
Myosin Heavy Chains
Rats
Swine
Tissue Engineering
Tissue Scaffolds
Troponin T