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.

Successfully developing tissue and organ equivalents requires one to balance device design strategies with the complexities of supporting cells able to accomplish targeted functions. For these equivalents to attain the goal of wide spread clinical use with off-the-shelf availability, it is also critical that methods for storing these systems are considered during in the design phase. This study presents a liver equivalent system — a radial flow bioreactor (RFB) — designed with each of these goals in mind. Its unique features include its capacity for cell support and the design of its cellular space. Specifically it is able to accommodate functional and reasonably sized tissue (more than 2×108 cells). The RFB’s effectiveness in supporting functioning liver cells; the consequences of the system’s flow on O2 transport; and the results of cryopreserving its tissue equivalents at sub-zero temperatures, are all presented.

Bioartificial Liver Devices (BALs) have the potential to serve as a bridge strategy for patients awaiting liver transplants, and also show promise as drug testing platforms for the pharmaceutical industry [1]. Yet the limitations of O2 transport through the 3D tissue structures of current designs continue to present engineering challenges. In previous work our group successfully improved O2 availability for hepatocytes by introducing micropathways within the BAL’s cellular space [3–5]. The current study investigates the benefits of increasing O2 availability of the flow medium via perfluorocarbons (PFCs). PFCs were chosen since they have demonstrated effectiveness in increasing the overall oxygen solubility of their carrier liquids, e.g., artificial blood [2]. The study seeks to clarify the effects of PFCs on hepatocyte viability and functional performance under various culture conditions.