Transmural flow bioreactor for vascular tissue engineering

Nutrient transport limitation remains a fundamental issue for in vitro culture of engineered tissues. In this study, perfusion bioreactor configurations were investigated to provide uniform delivery of oxygen to media equivalents (MEs) being developed as the basis for tissue‐engineered arteries. Bioreactor configurations were developed to evaluate oxygen delivery associated with complete transmural flow (through the wall of the ME), complete axial flow (through the lumen), and a combination of these flows. In addition, transport models of the different flow configurations were analyzed to determine the most uniform oxygen profile throughout the tissue, incorporating direct measurements of tissue hydraulic conductivity, cellular O2 consumption kinetics, and cell density along with ME physical dimensions. Model results indicate that dissolved oxygen (DO) uniformity is improved when a combination of transmural and axial flow is implemented; however, detrimental effects could occur due to lumenal pressure exceeding the burst pressure or damaging interstitial shear stress imparted by excessive transmural flow rates or decreasing hydraulic conductivity due to ME compaction. The model was verified by comparing predicted with measured outlet DO concentrations. Based on these results, the combination of a controlled transmural flow coupled with axial flow presents an attractive means to increase the transport of nutrients to cells within the cultured tissue to improve growth (increased cell and extracellular matrix concentrations) as well as uniformity. Biotechnol. Bioeng. 2009; 104: 1197–1206. © 2009 Wiley Periodicals, Inc.

[1]  G Saumon,et al.  A method for measuring the oxygen consumption of intact cell monolayers. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[2]  Jing Zhang,et al.  Novel intra-tissue perfusion system for culturing thick liver tissue. , 2007, Tissue engineering.

[3]  Jos Malda,et al.  The roles of hypoxia in the in vitro engineering of tissues. , 2007, Tissue engineering.

[4]  S. Munson-McGee.  An approximate analytical solution for the fluid dynamics of laminar flow in a porous tube , 2002 .

[5]  Hillel Laks,et al.  Analysis of oxygen transport in a diffusion‐limited model of engineered heart tissue , 2007, Biotechnology and bioengineering.

[6]  G. Weir,et al.  A stirred microchamber for oxygen consumption rate measurements with pancreatic islets , 2007, Biotechnology and bioengineering.

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

[8]  Robert M Nerem,et al.  Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells in an engineered tissue model of the aortic wall. , 2006, Biomaterials.

[9]  R T Tranquillo,et al.  A fibrin-based arterial media equivalent. , 2003, Journal of biomedical materials research. Part A.

[10]  Tetsuji Yamaoka,et al.  Three‐dimensional cell seeding and growth in radial‐flow perfusion bioreactor for in vitro tissue reconstruction , 2006, Biotechnology and bioengineering.

[11]  R. Tranquillo,et al.  ECM gene expression correlates with in vitro tissue growth and development in fibrin gel remodeled by neonatal smooth muscle cells. , 2003, Matrix biology : journal of the International Society for Matrix Biology.

[12]  J. Tramper,et al.  Oxygen gradients in tissue‐engineered Pegt/Pbt cartilaginous constructs: Measurement and modeling , 2004, Biotechnology and bioengineering.

[13]  R Langer,et al.  Morphologic and mechanical characteristics of engineered bovine arteries. , 2001, Journal of vascular surgery.

[14]  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.

[15]  R T Tranquillo,et al.  Fibrin as an alternative biopolymer to type-I collagen for the fabrication of a media equivalent. , 2002, Journal of biomedical materials research.

[16]  Diego Mantovani,et al.  Bioreactors for tissue engineering: focus on mechanical constraints. A comparative review. , 2006, Tissue engineering.

[17]  Milica Radisic,et al.  Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue , 2006, Biotechnology and bioengineering.

[18]  Manuel J T Carrondo,et al.  Biochemical engineering. , 2004, Current opinion in biotechnology.

[19]  Efstathios S Avgoustiniatos,et al.  Oxygen diffusion limitations in pancreatic islet culture and immunoisolation , 2002 .

[20]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[21]  John Aurie Dean,et al.  Lange's Handbook of Chemistry , 1978 .

[22]  R T Tranquillo,et al.  Enhanced fibrin remodeling in vitro with TGF-beta1, insulin and plasmin for improved tissue-equivalents. , 2002, Biomaterials.

[23]  D. Rumschitzki,et al.  Transport in rat vessel walls. I. Hydraulic conductivities of the aorta, pulmonary artery, and inferior vena cava with intact and denuded endothelia. , 2006, American journal of physiology. Heart and circulatory physiology.

[24]  Chrysanthi Williams,et al.  Endothelialization and Flow Conditioning of Fibrin-Based Media-Equivalents , 2006, Annals of Biomedical Engineering.

[25]  P. Arthur,et al.  Hibernation in Noncontracting Mammalian Cardiomyocytes , 2000, Circulation.

[26]  A. Grodzinsky,et al.  Fluorometric assay of DNA in cartilage explants using Hoechst 33258. , 1988, Analytical biochemistry.

[27]  Jennifer L. West,et al.  Physiologic Pulsatile Flow Bioreactor Conditioning of Poly(ethylene glycol)-based Tissue Engineered Vascular Grafts , 2007, Annals of Biomedical Engineering.

[28]  Christine A Curcio,et al.  Effects of particulates and lipids on the hydraulic conductivity of Matrigel. , 2008, Journal of applied physiology.

[29]  A. Mikos,et al.  Effect of convection on osteoblastic cell growth and function in biodegradable polymer foam scaffolds. , 2001, Biomaterials.

[30]  Chrysanthi Williams,et al.  Perfusion bioreactor for small diameter tissue-engineered arteries. , 2004, Tissue engineering.

[31]  R Langer,et al.  Functional arteries grown in vitro. , 1999, Science.

[32]  Milica Radisic,et al.  Medium perfusion enables engineering of compact and contractile cardiac tissue. , 2004, American journal of physiology. Heart and circulatory physiology.

[33]  C. Ellis,et al.  Oxygen diffusion and consumption of aortic valve cusps. , 2001, American journal of physiology. Heart and circulatory physiology.

[34]  Guillermo A. Ameer,et al.  In Vitro Characterization of a Compliant Biodegradable Scaffold with a Novel Bioreactor System , 2007, Annals of Biomedical Engineering.

[35]  Robert T Tranquillo,et al.  Cyclic distension of fibrin-based tissue constructs: Evidence of adaptation during growth of engineered connective tissue , 2008, Proceedings of the National Academy of Sciences.

[36]  Jan P Stegemann,et al.  Biomechanics and Mechanotransduction in Cells and Tissues Mechanical , biochemical , and extracellular matrix effects on vascular smooth muscle cell phenotype , 2005 .