Towards the biomimetic design of hollow fiber membrane bioreactors for bioartificial organs and tissue engineering: A micro-computed tomography (μCT) approach

Abstract

Hollow fiber membrane bioreactors (HFMBs) with cells cultured in the extracapillary space (ECS) have been proposed for bioartificial organs, to assist patients with failing organs, or to produce in vitro engineered biological substitutes of tissues and organs. They have not gained clinical acceptance yet. One factor limiting therapeutic application is the irregular membrane distribution in the HFMB shell, often considered a typical feature of clinical-scale HFMBs. Such distribution does not permit good control of shell spaces, prevents from offering cells a template structure mimicking the tissue-specific extracellular matrix (ECM) and an adequate supply of oxygen and nutrients, and limits control over cell migration, organization, and differentiation in the ECS. In this study, micro-computed tomography and image analysis techniques were used to characterize the space distribution in the shell of HFMBs varying for membrane packing density and bundling technique, and to investigate whether and how it is possible to manufacture HFMBs in which the distribution of intermembrane spaces in the ECS is uniform and biomimetic. Results suggest that the arrangement in HFMBs of hollow fiber membranes bundled in rolled cross-woven mats at high packing density permits to obtain a uniform shell-side membrane distribution with pore size distribution favoring cells migration around the membranes, and mimicking the ECM structure of bone tissue. • HFMBs were equipped with membranes in loose bundles or in cross-woven mats at varying packing density in the ECS. • Voids distribution in ECS was characterized by μCT and image analysis and was compared to natural bone and a synthetic bone substitute. • Results show that in HFMBs with densely packed membranes in cross-woven mats voids distribution is uniform and mimics bone ECM.