HIGHLY POROUS POLYMER MATRICES AS A 3-DIMENSIONAL CULTURE SYSTEM FOR HEPATOCYTES

Hepatocyte-based therapies (e.g., hepatocyte transplantation and extra corporeal support devices) may provide alternative therapies to treat patients with liver disease, but suitable approaches to localize these cells to a given location while maintaining liver-specific gene expre ssion must be developed, The suitability of highly porous three-dimens ional sponges fabricated from poly (L-lactic acid) [PLLA] as an hepato cyte culture system was evaluated in this study, Sponges were fabricat ed utilizing a particulate leaching technique, and were approximately 95% porous, with an average pore diameter of 180 mu m Hepatocytes seed ed into these sponges adhered and remained viable for 14 days, However , the secretion rate of albumin from these cells, an indication of liv er-specific gene expression, was low (approximately 6 pg/cell/day at d ay 1), and decreased steadily over the 14 days of the experiment, Coat ing sponges with collagen, and more preferably, immobilizing cells wit hin the PLLA sponges with a collagen gel, led to enhanced cell surviva l and albumin secretion at all time points, These data suggest that po rous PLLA sponges may provide a novel system for long-term culture of hepatocytes, and proper design of the system may allow the liver-speci fic gene expression of hepatocytes transplanted in these matrices to b e enhanced. (C) 1997 Elsevier Science Inc.