Modeling of flow‐induced shear stress applied on 3D cellular scaffolds: Implications for vascular tissue engineering

Novel tissue‐culture bioreactors employ flow‐induced shear stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex three‐dimensional (3D) microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear‐stress values within the physiological range of those naturally sensed by vascular cells (1–10 dyne/cm2), and will thereby provide suitable conditions for vascular tissue‐engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell‐layer thicknesses of 0, 50, 75, 100, and 125 µm. Four inlet velocities (0.5, 1, 1.5, and 2 cm/s) were applied to each model. Wall shear‐stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell‐layer thickness, and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in‐depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in vitro. Biotechnol. Bioeng. 2010; 105: 645–654. © 2009 Wiley Periodicals, Inc.

[1]  Randall M. German,et al.  Particle packing characteristics , 1989 .

[2]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[3]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[4]  L. Bonassar,et al.  Comparison of Chondrogensis in Static and Perfused Bioreactor Culture , 2000, Biotechnology progress.

[5]  John M. Tarbell,et al.  Effect of Fluid Flow on Smooth Muscle Cells in a 3-Dimensional Collagen Gel Model , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[6]  Antonios G. Mikos,et al.  Formation of highly porous biodegradable scaffolds for tissue engineering , 2000 .

[7]  G. B. Fiore,et al.  Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment , 2002, Biomechanics and modeling in mechanobiology.

[8]  L. Griffith,et al.  A microfabricated array bioreactor for perfused 3D liver culture. , 2002, Biotechnology and bioengineering.

[9]  Gordana Vunjak-Novakovic,et al.  Perfusion improves tissue architecture of engineered cardiac muscle. , 2002, Tissue engineering.

[10]  Brian P Helmke,et al.  Spatial microstimuli in endothelial mechanosignaling. , 2003, Circulation research.

[11]  Nitzan Resnick,et al.  Fluid shear stress and the vascular endothelium: for better and for worse. , 2003, Progress in biophysics and molecular biology.

[12]  M. Swartz,et al.  Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model. , 2003, American journal of physiology. Heart and circulatory physiology.

[13]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[14]  K. Tanishita,et al.  Effect of shear stress on microvessel network formation of endothelial cells with in vitro three-dimensional model. , 2004, American journal of physiology. Heart and circulatory physiology.

[15]  Melody A Swartz,et al.  Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. , 2004, Microvascular research.

[16]  Jenneke Klein-Nulend,et al.  A comparison of strain and fluid shear stress in stimulating bone cell responses—a computational and experimental study , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[18]  L. Draghi,et al.  Microspheres leaching for scaffold porosity control , 2005, Journal of materials science. Materials in medicine.

[19]  Margherita Cioffi,et al.  The effect of hydrodynamic shear on 3D engineered chondrocyte systems subject to direct perfusion. , 2006, Biorheology.

[20]  F. Boschetti,et al.  Prediction of the micro-fluid dynamic environment imposed to three-dimensional engineered cell systems in bioreactors. , 2006, Journal of biomechanics.

[21]  Gabriele Dubini,et al.  Modeling evaluation of the fluid-dynamic microenvironment in tissue-engineered constructs: a micro-CT based model. , 2006, Biotechnology and bioengineering.

[22]  Tal Dvir,et al.  A novel perfusion bioreactor providing a homogenous milieu for tissue regeneration. , 2006, Tissue engineering.

[23]  C P Chen,et al.  Enhancement of cell growth in tissue‐engineering constructs under direct perfusion: Modeling and simulation , 2007, Biotechnology and bioengineering.

[24]  Shulamit Levenberg,et al.  Tissue Engineering of Vascularized Cardiac Muscle From Human Embryonic Stem Cells , 2007, Circulation research.

[25]  Harmeet Singh,et al.  Computational fluid dynamics for improved bioreactor design and 3D culture. , 2008, Trends in biotechnology.

[26]  Niamh Plunkett,et al.  Bioreactors in tissue engineering. , 2011, Technology and health care : official journal of the European Society for Engineering and Medicine.