As part of the quest to create artificial organs, emerging microfabrication techniques are enabling researchers to construct complex architectures to stimulate cell function.
As bodily organs go, the liver is the great generalist. Whereas a lung or a kidney essentially performs one important function, the liver is a jack-of-all-trades, responsible for various metabolic and nutrient-storage activities, filtering of blood impurities and detoxification of foreign compounds, production of bile for digestion, maintenance of electrolyte and water balance, and secretion of diverse serum proteins and enzymes, among other chores. As self-sufficient as it is versatile, the liver regenerates its own tissue faster than any other organ and can function with as little as one-fifth of its original mass. Despite these apparently robust attributes, however, liver failure kills more than 30,000 patients each year in the United States, with ten times that number admitted to hospitals for transient liver problems.
Because so many functions of the liver are critical for survival, researchers have developed several cell-based approaches to augment traditional supportive therapies that essentially comprise the administration of fluids and intensive monitoring. These include transplanting liver cells by injecting them into the bloodstream, developing liver tissue substitutes for implantation, and creating extracorporeal circuits containing live cells used to "process" a patient's blood. A limiting factor in each of these methods is the difficulty of making the cells function the same way in isolation as they do in the liver.
Among the scientists investigating the functionality of harvested cells as part of the fundamental effort to create viable artificial liver devices is Sangeeta Bhatia, assistant professor of bioengineering at the University of California at San Diego Jacobs School of Engineering. In 1998, Bhatia patented a microfabrication technique that made it possible to assemble various liver cells on glass chips, in a manner similar to the assembly of integrated circuits on silicon. The key finding was that the spatial arrangement of different cells was critical to their function and interaction: for example, that hepatocyte function improves when cells are located beside fibroblasts, which constitute the membrane around the liver. In fact, Bhatia has demonstrated that certain harvested liver cells can be induced to function at levels significantly higher (as much as 5 to 10 times higher) than in the body, opening the door to future devices with hyperefficient cellular components.
Bhatia has employed a range of microfabrication tools in the attempt to reproduce distinct hepatic tissue architectures. These techniques include soft lithography (to make minuscule polymer structures), photolithography (for patterning using semiconductor technology), and electrochemical etching (to interface cells with silicon chips). This last process involves growing liver cells in individually etched silicon pores to produce a kind of "micro-bioreactor" that would be part of an extracorporeal device. According to Bhatia, the significance of the work is that "it allows for a transition from two-dimensional to three-dimensional studies of structure and function, and reveals how to best house the cells."
Should a better understanding of the tissue microenvironment lead to the fabrication of effective external artificial liver devices, how might they be used? Because many patients die while awaiting transplantation, one application would certainly be as a bridge to a first or second transplant. But the ultimate goal, says Bhatia, would be to harness the liver's remarkable regenerative powers and avoid transplants altogether—to use a functional extracorporeal device "to keep patients alive long enough for their own liver to recover." It is the quest for such quality temporary housing that keeps Bhatia's construction crew working overtime.