Ensure Practical Surgical Implantation

The key requirements for ensuring practical surgical implantation of a bioartificial pancreas are:

Islet density must be high

And therefore the size of the sheet must not be too large. To minimize trauma, the volume of the final implant should be minimized—as a rule only 2 to 5 times the volume of the islet. Some devices are mostly “dead space” and therefore are too large for convenient implantation.

The Islet Sheet can be made to a very high islet cell density: at least 35 percent islets. The photo below shows lightly colored islets crowded close together in the sheet. The fibers are strands of the paper mesh used to strengthen the sheet and permit it to be sutured in place.

Similarly, the electron micrograph micrograph below shows that about a third of the volume of the sheet consists of islets of Langerhans.

Sheet must be biostable, chemically and physically durable, and retrievable

The immunoisolation membrane must remain chemically unchanged in the presence of cells and intercellular fluid. For instance, polyethylene glycol is broken down in a few months by the body. Islet Sheets are made of alginates which have been demonstrated to be stable for years in vivo. The device must be resistant to cracking and breaking from mechanical stress.

The device should be retrievable if the graft fails. The recent history of disease caused by failed breast implants has increased the value of retrievable immune barriers such as the Islet Sheet.

The Islet Sheet is biostable, durable and retrievable. The first photo below shows a sheet just after it was sutured to the pancreas of a dog. In the second image, the same sheet is shown nine weeks later. It remains intact and could be removed from the pancreas by clipping the sutures. This remarkable absence of a significant foreign body response has been repeated in many subsequent experiments—most recently in Fisher rats, a strain known to have an unusually active foreign body response.

Sheet must be surgically acceptable

Islets of Langerhans have been implanted into hundreds of diabetics. By far the most common choice is infusion into the portal vein. In Figure xx, the hepatic artery and vein are shown in red and dark blue, and the bile duct in green. The portal vein, light blue, drains the abdominal viscera, bringing all the blood from the intestines (with newly absorbed food and, incidentally, oral drugs) directly to the liver. A syringe is used to infuse isolated islets. They travel with the portal blood and lodge in the liver. They have been shown to be there, functioning, years later.

The size of the Islet Sheet prohibits portal infusion. The sheet needs to lie against well- vascularized tissue. Figure xx shows the major organs of the abdomen. The sheet could be placed against any of them. The sheet may also be implanted under the skin.