Use of perfluorocarbons to enhance the performance of perfused three‐dimensional hepatic cultures

Abstract

Bioartificial liver devices (BALs) are extracorporeal systems designed to temporarily bridge patients until a suitable donated liver is available for transplantation and also have value for pharmaceutical testing applications. Yet critical issues exist that limit the functional performance of their current designs. One of these concerns scale up issues connected to oxygen (O2 ) delivery to the cells housed within their three-dimensional (3D) configurations, and its consequences to device performance. As primary blood substitute candidates with extraordinarily high O2 capacity, perfluorocarbons (PFCs) offer hope as one strategy for addressing the O2 delivery issue encountered when scaling up the tissue space of current BAL designs. This study utilizes a PFC-based second-generation O2 carrier OXYCYTE®, as an additive to regular nutrient medium, for augmenting O2 delivery in a customized 3D tissue assembly system. The results demonstrate that the addition of PFCs significantly increases the O2 capacity of regular medium and that net cytochrome P450 activity levels are considerably increased under flow in PFC-treated systems, as compared to controls. This work thus clarifies the benefits of using PFCs to enhance the functional performance of 3D liver systems.

Oxygen delivering biomaterials for tissue engineering

“…Other studies using similar bioreactor setups have also found that supplementing culture medium with PFC emulsions improved cell viability, differentiation, and function for tracheal and hepatic tissue constructs. 46,47 However, one of these studies found that adding PFC emulsions to their bioreactor setup decreased chondrogenesis in the cartilaginous layer of tracheal constructs. Thus, supplementing culture medium with PFC emulsions may only benefit specific cell types.…”

“…Incorporation of solid peroxides in synthetic scaffolds for dermal, pancreatic, skeletal muscle, and general TE applications 42–47 …”

Reduction of oxygen inhibition effect for microalgal growth using fluoroalkylated methoxy polyethylene glycol-stabilized perfluorocarbon nano-oxygen carriers

“…Perfluorocarbon (PFC), a fluorine-substituted derivative of hydrocarbons, can dissolve large respiratory and other non-polar gases as compared to water [26], exhibiting a great potential for use as an oxygen transporter. PFCs have been widely used in medical applications to deliver oxygen to mammalian tissues and/or remove metabolically waste as so-called blood substitutes [27,28]. Additionally, using PFCs as oxygen carriers to enhance the efficiency of microbial, plant or animal cell growth has also been extensively reported in the past two decades [29][30][31].…”

A 3D Cell Culture Organ-on-a-Chip Platform With a Breathable Hemoglobin Analogue Augments and Extends Primary Human Hepatocyte Functions in vitro

“…This approach has been used successfully in bioartificial liver bioreactors to meet hepatocyte oxygen demands and preserve differentiated phenotypes (Nieuwoudt et al, 2005;Kinasiewicz et al, 2008;Nieuwoudt et al, 2009). Unfortunately, common oxygen carriers in vivo and in vitro are emulsified perfluorocarbons (PFC) that, as emulsions, require excessive equipment in order to charge them with oxygen (Shi and Coger, 2013), and are thus not readily amenable to multi-well plate based cell culture and drug testing methodologies.…”