Design criteria for a modular tissue-engineered construct.

A modular construct, created by the assembly of discrete microscale objects, has been proposed to enable the engineering of large, vascularized tissues containing multiple cell types. A simple theoretical analysis of the design constraints relevant to a modular construct was performed and used to define useable device operating ranges. The analysis assumed that the primary design constraint was the operating wall shear stress that would lead to a non-thrombogenic endothelial cell layer. At the lower end of the desirable shear range, oxygen depletion (over the length of the construct) limited the maximum allowed construct length, whereas at the upper end of this shear range, construct pressure difference limited maximum construct length. To compare with the theoretical analysis, real constructs were assembled, and construct porosity was assessed using superficial velocity-pressure difference profiles. Significant deviations from ideal construct porosity were observed for soft collagen gel constructs. Improvement of the module mechanical properties through the use of poloxamine instead of collagen as the module material enabled constructs closer to the ideal case to be assembled. With such improvements, modular tissue engineering offers a feasible strategy for the development of clinically significant whole-organ replacements.

[1]  Lounes Tadrist,et al.  Experimental analysis of the porosity of randomly packed rigid fibers , 1999 .

[2]  H. Jaeger,et al.  Physics of the Granular State , 1992, Science.

[3]  Larry V. McIntire,et al.  DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Robert N. Maddox,et al.  Mass Transfer: Fundamentals and Applications , 1984 .

[5]  L V McIntire,et al.  Shear stress and cyclic strain modulation of gene expression in vascular endothelial cells. , 1995, Blood purification.

[6]  Alison P McGuigan,et al.  Vascularized Organoid Engineered by Modular Assembly Enables Blood Perfusion , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  L. McIntire,et al.  Mechanical effects on endothelial cell morphology: In vitro assessment , 1986, In Vitro Cellular & Developmental Biology.

[8]  E. C. Albritton Standard values in blood. Being the first fascicle of a handbook of biological data. , 1952 .

[9]  Michael V Sefton,et al.  Semi-synthetic collagen/poloxamine matrices for tissue engineering. , 2005, Biomaterials.

[10]  Laura E Niklason,et al.  Requirements for growing tissue-engineered vascular grafts. , 2003, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[11]  H. Kaufmann,et al.  The Liver: Biology and Pathobiology, 2nd ed , 1989 .

[12]  R. Fournier Basic Transport Phenomena In Biomedical Engineering , 1998 .

[13]  Robert K. Niven,et al.  Physical insight into the Ergun and Wen & Yu equations for fluid flow in packed and fluidised beds , 2002 .

[14]  R. Tompkins,et al.  Oxygen uptake rates in cultured rat hepatocytes. , 1992, Biotechnology and bioengineering.

[15]  J. Milewski The Combined Packing of Rods and Spheres in Reinforcing Plastics , 1978 .

[16]  S. Ergun,et al.  Fluid Flow through Randomly Packed Columns and Fluidized Beds , 1949 .

[17]  L. McIntire,et al.  Response of cultured endothelial cells to steady flow. , 1984, Microvascular research.