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By Karla Gale

WESTPORT, CT (Reuters Health) – Bioengineers have developed an implantable capsule that can release a steady supply of insulin into the bloodstream. The pore size of these biocapsules is controlled so that the cells inside are protected from cellular and humoral components of the immune system, explained Drs. Lara Leoni and Tejal A. Desai of the University of Illinois at Chicago.

The investigators used "bulk and surface micromachining and microfabrication" to develop biochemically inert, relatively strong membranes of silicon and its oxides and nitrides. Pore thicknesses were 24.5 nm, smaller than the 30 nm required to be impervious to immunoglobulins and complement molecules, they report in the November issue of IEEE Transactions on Biomedical Engineering.

In addition, "the biocapsule surface repels unwanted cells or proteins, in order to prevent biofouling from clogging the pores," Dr. Desai told Reuters Health.

Placement of the membrane into diffusion chambers demonstrated that glucose could pass through with near-linear diffusion kinetics, and that glucose transport was not inhibited by the presence of albumin. Insulin was also able to diffuse across the chamber following an initial lag.

The biocapsules were seeded with cultured mouse insulinoma cells at a concentration of about 3500 cells/capsule. When cells alone were introduced into the capsules, aggregates formed that became hypoxic in the center and showed signs of necrosis.

To prevent this from happening, cells were embedded in collagen or a collagen-chitosan matrix. The capsules were able to secrete insulin, with the higher rate associated with the collagen matrix. While the cells were viable, their ability to proliferate was inhibited.

"Being able to control cell proliferation while keeping the cells viable and secreting would be a major step toward the design of a well-controlled immunoisolation system," Drs. Leoni and Desai note.

Dr. Desai said her team has implanted biocapsules in small animals and they have observed "some short-term success." When the development has reached the clinical trial stage, the biocapsules will probably be seeded with primary pancreatic cells, she added.

"If you use primary pancreatic cells, as long as those cells get nutrients and oxygen within that capsule, they stay alive indefinitely–much as they do in the normal body," Dr. Desai said.

"We think this is exciting because it's one of the first applications of nanotechnology to this area," she said, noting that there are other potential applications as well. Another application her team is working on involves neurosecretory cells for the treatment disorders such as Alzheimer's disease and Parkinson's disease.