Liver cells thrive on novel silicon chips

In a feat that could lead to new medical treatments, researchers have grown healthy liver cells on silicon chips.

Silicon bioreactor, in which circular wells hold liver cells. Ned Jastromb/UCSD

Called a “liver bioreactor,” the apparatus consists of a chip of spongelike silicon with pores just 2 to 1,500 nanometers wide. The research team, from the University of California, San Diego (UCSD), used electrochemistry to etch the pores and then circuit-making techniques to add 15-micron-wide wells, each just big enough to house a rat liver cell.

The liver’s primary cells, hepatocytes, are notoriously hard to culture. But when grown in the bioreactors, thousands of the cells functioned normally throughout a 2-week trial, the researchers reported last week in San Diego at a meeting of the American Chemical Society.

Pores of certain sizes provide a texture on which cells thrive, graduate student Vicki Chin found. “It’s kind of like the Goldilocks principle,” says chemist Michael J. Sailor, a member of the team. “Some of these holes are too big, some too small, and some are just right.”

Pores may also allow the transfer of nutrients between cells while keeping out large objects, such as bacteria, suggest the researchers.

It might be possible to exploit silicon’s electronic properties by building sensors and other components directly into the bioreactor. Such a device could monitor the cells’ health, says Sailor, whose lab made the porous chips under the direction of UCSD researcher Boyce E. Collins. “We want to have some way for these cells to report to us and tell us whether they’re happy or not,” says Sailor.

Integrating microelectronics and biomedicine to read cellular signals and to respond appropriately, such as with a drug dose, is “the Holy Grail of this field,” says engineer Philippe M. Fauchet, director of the Center for Future Health at the University of Rochester in New York.

Efforts to combine cells with porous silicon received a boost in the mid-1990s. That’s when Leigh Canham of the British defense-research agency DERA discovered that some porous silicon is as compatible with the body as titanium, the stuff of artificial hips. In contrast, living tissues reject nonporous silicon.

“Silicon, surprisingly, is an ideal material for a new generation of reactors,” says Sangeeta N. Bhatia, a physician and bioengineer on the UCSD team.

Bhatia hopes that such bioreactors eventually could become the basis of artificial livers. “Porous silicon is quite attractive as a biodegradable scaffold” on which such an organ replacement could be built, adds Canham, who has just joined a company developing biologically compatible silicon structures.

By 2010, the worldwide incidence of the hepatitis C infection probably will overtake that of HIV, says Bhatia. Yet the standard treatment for liver disease is transplantation, and fewer livers are available than are needed now, she says.

Bhatia suspects that the first use of the bioreactor might be for testing pharmaceuticals’ toxicity, potentially even replacing laboratory animals, Bhatia says.

Fauchet says that such testing would help speed the screening of drug candidates. One potential pitfall to consider, he cautions, is that subtle changes in cells grown on silicon may not necessarily reflect the behavior of comparable cells in the body.

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