Design Criteria for a Modular Tissue-Engineered Construct

Abstract

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.