Myocardial Scaffold-Based Cardiac Tissue Engineering: Application of Coordinated Mechanical and Electrical Stimulations

Abstract

Recently, we have developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserved natural extracellular matrix structure, mechanical anisotropy, and vasculature templates, and also showed good cell recellularization and differentiation potential. In this study, a multi-stimulation bioreactor was built to provide coordinated mechanical and electrical stimulations for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (106 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-day culture 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 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-day bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2-day and 4-day tissue constructs were comparable to the tissue constructs produced by stirring reseeding followed by 2-week static culture, 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.

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

“…Though bioreactors that have both electrical and mechanical stimulation capabilities have been created previously, 14,25,26 to date, only one study has looked into the effects of combined electromechanical stimulation in cardiac engineered tissue. 27 In this study, Wang et al observed that electromechanical stimulation improved cardiac differentiation of mesenchymal stem cells and an increase in contractile proteins, such as a-actinin, myosin heavy chain, and connexin 43 (Cx43), as compared with those cultured statically. However, the electrical and mechanical stimulation were applied simultaneously, which is not physiologically relevant in the context of the heart, where mechanical stimulation represents the filling of the ventricles with blood and electrical stimulation of the ventricles to contract occurs just before the release of stretch.…”

Self-doped polyaniline-based interdigitated electrodes for electrical stimulation of osteoblast cell lines

“…Electrical charges play an important role in stimulating either the proliferation or differentiation of various cell types [2][3][4]. Both in-vivo and in-vitro studies have demonstrated that electrical stimulation, either in AC, DC, or pulsed electromagnetic field can stimulate cell growth or bone regeneration [5][6][7].…”

Coming to terms with tissue engineering and regenerative medicine in the lung

“…However, realization of this potential will be dependent on the ability of MSCs to recapitulate both anatomical and functional features of the different lung cell types. There is now considerable evidence that MSCs play a role in regeneration and repair (61,62,81,91,112,201) and in secretion of growth factors, immune modulators, and other factors that support the idea that MSCs may be better taken up in organ scaffolds (158,198,220), especially if scaffolds enhance their differentiation (86,219), presumably through cell-matrix interactions (64,161,174,232). Several studies have shown that MSCs can attach and proliferate in lung scaffolds (39,117,131,137).…”