Table 1: Bioreactor technology for cardiac tissue engineering.

AuthorsYearCell sourceScaffoldBiophysical stimulusApparatusBiological effects

Vandenburgh et al. [38]1996Neonatal rat cardiomyocytes Collagen-coated silicon membranesUnidirectional stretchMechanical cell stimulator Increased foetal - and adult -MHC isoforms

Carrier et al. [40]1999Neonatal rat and embryonic chick cardiomyocytesPGAPerfusion by medium mixingRotating vessel microgravity bioreactor Expression of cardiac-specific proteins and better ultrastructural organization

Fink et al. [41]2000Neonatal rat and embryonic chick cardiomyocytesCollagen IUnidirectional stretchCustom stretching deviceImproved organization of cardiomyocytes; hypertrophy

Akhyari et al. [42]2002Human heart cells (ventricular biopsy)Gelfoam gelatineCyclic stretchBiostretch Enhancement of collagen matrix formation and organization

Zimmermann et al. [43]2002Neonatal rat cardiomyocytesCollagenUnidirectional cyclic stretchCustom stretching deviceHighly organized sarcomeres; adherens junctions, gap junctions, and desmosomes; well-developed T-tubular network; contractile characteristics of native myocardium

Iijima et al. [44]2003Rat cardiomyocytes and skeletal myocytes Collagen-coated silicon membranesCyclic stretchMechanical cell stimulatorExpression of cardiac-specific proteins: cardiac troponin T, cadherin, and connexin 43

Radisic et al. [45]2004Neonatal rat cardiomyocytesUltrafoam collagenPerfusionCustom deviceThick, compact, and contractile cardiac constructs; higher cell viability

Boublik et al. [46]2005Rat heart cellsHyaluronanCyclic stretchBiostretchHybrid cardiac constructs with mechanical properties suitable for in vitro loading studies and in vivo implantation

Feng et al. [47]2005Neonatal rat cardiomyocytesSilicon membranesMechanical stretch (+ electric field stimulation)Custom stretching deviceIn vitro simulation of the electrical and mechanical responses of the myocardium in vivo

Figallo et al. [48]2007Neonatal rat cardiomyocytes and human ESCsCollagen-coated glassPerfusionCustom microarray (MBA)Increased smooth muscle actin and cell density

Brown et al. [49]2008Neonatal rat cardiomyocytesUltrafoam collagenPerfusionCustom deviceEnhancement of contractile properties

Gwak et al. [50]2008Mouse ESC-derived cardiomyocytesPLCL and PLGACyclic stretchCustom device Enhancement of cardiac-specific gene expression: -MHC, -actin

Shimko and Claycomb [51]2008Mouse ESC-derived cardiomyocytesCollagen I/fibronectinUnidirectional cyclic stretchCustom stretching device Increased gene expression at 3 Hz cyclical stretch

Ge et al. [52]2009Rat BM-MSCsSilicon membraneBiaxial mechanical stretchCustom stretching device Expression of -actin, connexion 43, -MHC, and troponin I

Barash et al. [53]2010Neonatal rat cardiomyocytesAlginatePerfusion (+ electric field stimulation)Custom device Promotion of cell elongation and striation and enhancement of the expression level of connexin-43

Hosseinkhani et al. [54]2010Rat CSCsCollagen-PGA nanofibersPerfusionCustom deviceSignificant enhancement of cell proliferation

Salameh et al. [55]2010 Neonatal rat cardiomyocytesGelatin-coated silicone membraneBiaxial mechanical stretchFlexcell Tension System FX-4000 Self-organization of cardiomyocytes, enhanced connexin-43 expression and distribution at the cell poles

Galie and Stegemann [56]2011Rat cardiac fibroblasts Collagen hydrogelMechanical stretch and interstitial flowCustom deviceCell viability

Hollweck et al. [57]2011Human UCMSCsPTFEBiaxial mechanical stretchCustom deviceConfluent cellular coating without damage on the cell surface

Kenar et al. [58]2011Human MSCs (Wharton’s Jelly)PHBV-PLLA and PGSPerfusionCustom deviceEnhanced cell viability, uniform cell distribution and alignment

Kensah et al. [59]2011Neonatal rat cardiomyocytesCollagen I/MatrigelCyclic stretch and perfusion (+ electric field stimulation)Custom deviceCardiomyocyte hypertrophy, shift of myosin heavy chain expression from the alpha to beta isoform

Maul et al. [60]2011Rat MSCs Collagen-coated silicon membranesBiaxial mechanical stretch () or laminar shear stress (*) or cyclic hydrostatic pressure (#)() Flexcell Tension System FX-4000 or (*) Streamer shear stress Flexcell device or (#) custom deviceSystematic examination of the effects of mechanical stimulation on MSCs

Tulloch et al. [61]2011Human ESCs and human induced pluripotent stem cell-derived cardiomyocytesCollagen I Cyclic stressFlexcell Tension System FX-4000 Cardiomyocytes hypertrophy and proliferation

Govoni et al. [62]2012Rat MSCsHyaluronanUnidirectional cyclic stretchCustom deviceCell multilayer organization and invasion of the 3D mesh of the scaffold, muscle protein expression

Maidhof et al. [63]2012Rat heart cellsPGSPerfusion (+ electric field stimulation)Custom deviceImprovement of DNA content, cell distribution throughout the scaffold thickness, cardiac protein expression, and cell morphology

Shachar et al. [64]2012Neonatal rat cardiomyocytesRGD-attached alginateCompression and shear stressCustom deviceIncreased connexin-43, -actin, and N-cadherin