Research Project
6142043
The overall goal is to develop a viable extracorporeal system for sustaining liver cells and liver cell function. While many investigators have attempted to replace liver function with cell transplantation or extracorporeal devices, the only successful long-term replacement has been liver transplants. A device, capable of supporting hepatocyte function, would have immense value for patients awaiting a liver transplant or those undergoing liver regeneration following acute liver failure. The goal of this project is to develop and demonstrate the success of a set of in vitro conditions suitable for supporting hepatocyte function. Specific aims of this proposal are described. Since biocompatibility of hepatocytes with poly(lactic-co-glycolic) acid (PGLA) as a solid substrate has already been demonstrated, the first aim of this work is to promote cell adhesion to PGLA-based 3-D foams using a series of surface treatments including plasma and chemical treatment of PGLA. The second aim is to test three-dimensional foams of PGLA which support hepatocyte function in a flow-through system. This is a necessary step towards the fabrication of an extracorporeal device. PGLA foams provide a unique substrate for cell survival, i.e., one that is biocompatible, contains appropriately large pores to maintain functioning cells, and is porous enough to allow nutrients and waste to percolate through it. For Phase II, a strategy will be developed to engineer the physical parameters of the foams in order to develop a working device. Such a device will need to be capable of supporting 200 x 10^9 cells for an extended period of time. PROPOSED COMMERCIAL APPLICATIONS: This work is significant as a means toward developing an extracorporeal device for patients suffering acute liver failure. It will temporarily replace liver function while liver regeneration occurs for patients awaiting a liver transplant.
