Transport Analysis of Engineered Liver Tissue Fabricated Using a Capsule-Based, Modular Approach

Annals of Biomedical Engineering
Ramkumar T Annamalai, H W Matthew

Abstract

The bioinspired, microscale tissue engineering approach has emerged in recent years as a promising alternative to preformed scaffolds. Using this approach, complex tissues and organs can be efficiently engineered from microscale modules to replicate the intricate architecture and physiology of vascularized organs and tissues. Previously, we demonstrated assembly of a prototype, engineered liver tissue, formed by the fusion of hepatocyte-containing capsules. Here, we analyzed the effects of various controllable system parameters with the aim of predicting the operating limits of our modular tissue in high cell density, perfused cultures. Both the capsule diameter and construct height were limited by mass transfer requirements, while the shear stress on the capsule wall and the pressure drop across the packed capsule bed were dictated by the capsule diameter and permissible flow rates of the system. Our analysis predicts that capsules with a 200 µm radius can efficiently maintain hepatocytes at cell densities comparable to liver tissue. Some model predictions were validated by packed bed perfusion cultures. Flow-induced bed compaction hysteresis was tested experimentally and found to have minimal effect on flow characteristics. T...Continue Reading

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