New advances in MR‐compatible bioartificial liver

Abstract

MR-compatible bioartificial liver (BAL) studies have been performed for 30 years and are reviewed. There are two types of study: (i) metabolism and drug studies using multinuclear MRS; primarily short-term (< 8 h) studies; (ii) the use of multinuclear MRS and MRI to noninvasively define the features and functions of BAL systems for long-term liver tissue engineering. In the latter, these systems often undergo not only modification of the perfusion system, but also the construction of MR radiofrequency probes around the bioreactor. We present novel MR-compatible BALs and the use of multinuclear MRS (13C, 19F, 31P) for the noninvasive monitoring of their growth, metabolism and viability, as well as 1H MRI methods for the determination of flow profiles, diffusion, cell distribution, quality assurance and bioreactor integrity. Finally, a simple flexible coil design and circuit, and life support system, are described that can make almost any BAL MR-compatible.

In vitro models for liver toxicity testing

“…Another device used microcarriers and alginate to allow for a large number of cells, minimal migration, and sufficient oxygen diffusion. 94 …”

Polymeric hollow fiber membranes for bioartificial organs and tissue engineering applications

“…Some examples such as bioartificial liver (BAL), bioartificial pancreas (BAP) and bioartificial kidney (BAK) are collected in Table . Extensive reviews on BAL, BAK and general bio‐hybrid organs for patient therapy have been published, and thus, the reader is referred to those works. Here, we discuss certain aspects related to the HF membranes.…”

Effect of Oxygen Concentration on Viability and Metabolism in a Fluidized-Bed Bioartificial Liver Using 31P and 13C NMR Spectroscopy

“…[1][2][3][4][5][6][7][8] NMR spectroscopic analysis of BALs permit noninvasive quantification of viability and metabolic functions. 9 In conjunction with a fluidized-bed bioreactor, thorough mixing of oxygen within the perfusion chamber eliminates stagnant zones insuring oxygen homogeneity. 8,10 Therefore, in this study, we combine these two technologies to determine the effect of oxygen in a well-mixed fluidized bed.…”

“…13 Historically, 3D membrane-type BAL studies have used higher oxygen levels in media to traverse the larger diffusion distances without the aid of oxygen carriers, 9,[15][16][17][18][19] whereas lower oxygen concentrations have been used with microcarrier [20][21][22] and flatbed 1,3,10,[23][24][25] BAL designs, where the majority of hepatocyte reside at the medium-surface interface. The encapsulate type of BALs have seen a full range of oxygen concentrations used, making this category the most variable in terms of oxygen concentration in the literature.…”

“…Four oxygen treatments (95%, 50%, 35%, and 20%) were tested for maintaining viability using in vivo 31 P NMR spectroscopy to noninvasively monitored b-nucleotide triphosphate (NTP) levels, a direct measure of viability. 9,29,30 In vivo 13 C NMR spectroscopy noninvasively monitored metabolism of 4 mM 2-13 C-glycine, 4 mM U-13 C-glutamine, and 25 mM 2-13 C-glucose, which replaced their 12 C analog in the media. The oxygen levels used in this study span those used in the literature 8,10,[26][27][28] and are used to demonstrate the use of the noninvasive NMR spectroscopy methodology, as it relates to BAL research and development.…”