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

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. The effectiveness factor (η) for the overall oxygen transfer within packed beds of capsule modules was estimated to be 0.72 for all conditions. Primary hepatocytes encapsulated in the capsules exhibited normal metabolism and formed spheroids during a 7-day culture. The model predictions can be useful to study mass transfer and shear stress in high-density perfusion cultures. Overall, analysis of a perfused, capsule-based, modular tissue demonstrated the feasibility of the technology as a platform for fabrication of highly metabolic solid organs.

journal_name

Ann Biomed Eng

authors

Annamalai RT,Matthew HWT

doi

10.1007/s10439-018-02192-y

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

1223-1236

issue

5

eissn

0090-6964

issn

1573-9686

pii

10.1007/s10439-018-02192-y

journal_volume

47

pub_type

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