46WWW.CEN-ONLINE.ORG MAY 5, 2008

PRICK FINGER. Test blood. Inject insulin. For millions of people around the world, this painful and tedious cycle is all that stands between relative health and the rav-ages of diabetes, a disease known to cause blindness, kidney failure, and death. Joseph P. Kennedy hopes that a specially coated metal tube, no larger than a cigarette, will someday put an end to all that.

Kennedy, a professor of chemistry and polymer science at the University of Akron, in Ohio, calls the device a bioartificial pan-creas. He spoke about its construction dur-ing a presentation in the Division of Polymer Chemistry at the American Chemical Society national meeting in New Orleans last month.

The World Health Organization estimates that more than 180 mil-lion people worldwide have diabe-tes, and that number is expected to double by 2030. An artificial pancreas, Kennedy says, “would have immense socioeconomic significance.”

A number of research groups around the world are currently working to develop artificial pan-creas technologies. Most strate-gies involve transplanting healthy islets—the pancreatic cells that de-tect glucose and release insulin—into the diabetic patient. The cells

are encapsulated either individually within a hydrogel or as a large collection of cells within some type of polymer membrane.

Kennedy’s group takes the latter ap-proach. Their prototype begins with a scaffold made from a 7-cm-long tube of the biocompatible nickel-titanium alloy nitinol that’s been perforated with laser-cut hex-agonal holes. Polyurethane nanofibers are then electrospun over the tube, through

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SCIENCE & TECHNOLOGY

PERFECTING AN ARTIFICIAL PANCREAS

ACS MEETING NEWS: Specialized polymer is key to insulin-regulating device

INSULIN REGULATOR

The bioartificial pancreas and a close-up of its polymer-coated mesh.

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47WWW.CEN-ONLINE.ORG MAY 5, 2008

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techniques designed by Kennedy’s colleague Miko Cakmak, who is a polymer engineering professor at Akron. The resulting entangle-ment of nanofibers, or so-called nanomats, reinforces the open-ings in the scaffold’s mesh.

THE TUBE is then coated with a semipermeable polymer mem-brane made up of poly(dimethylacrylamide) and polydimethylsi-loxane domains cross-linked by polymethylhydrosiloxane. The en-tire assembly is dried, washed to remove small molecules, cleaned in an autoclave, and finally filled with a suspension of pig islets.

Ken S. Rosenthal, a professor of microbiology and immunology at Northeastern Ohio Universities College of Medicine, and one of Kennedy’s collaborators on the project, says that the polymer mem-brane is really what sets this artificial pancreas apart. Encapsulating a large collection of islets has been difficult, he says, because the ma-terial to make that capsule has never been designed for that purpose.

“This device differs because its polymer membrane has been designed to have the optimal properties for encapsulating islets,” Rosenthal tells C&EN. “It allows for free movement of insulin and glucose but restricts access of immune molecules that might at-tack the encapsulated islets.” Likewise, any viruses that might be piggybacking on the islets are trapped behind the membrane.

“Because of that, we can use pig cells, and the only thing that communicates between them and the patient are the small mol-ecules and small proteins,” Rosenthal notes.

The polymer can also sequester oxygen from the environment, thanks to its silicone-based components. This oxygen nourishes the encapsulated islets cells. “These membranes are biocompat-ible, flexible, transparent, autoclavable, and they’re easily synthe-sized and relatively inexpensive,” Rosenthal says.

“Kennedy is the only researcher that I know of who designed the bioartificial pancreas for longevity and oxygen permeability,” says Len Pinchuk, president and chief executive officer of Miami-based Innovia, a company that develops biomaterials and medical devices. “Most other researchers in this field come from a biological back-ground and don’t have the tools to create these new biomaterials.”

The artificial pancreas can be inserted anywhere in the body that encounters blood flow, Kennedy says, even just beneath the skin. “The blood brings the oxygen and nutrients needed by the islets and removes metabolic wastes, such as carbon dioxide.”

The device, Kennedy notes, acts as both a glucose sensor and an insulin delivery device. “It delivers exactly the needed amount of insulin,” he says. “Insulin concentration in the body must be pre-cisely controlled. Too high or too low concentrations result in very serious side effects.”

People with type 1 diabetes—around 2 million in the U.S. alone—make up the primary market for the device, although Kennedy thinks it could also be useful for the some 4 million patients with type 2 diabetes who inject insulin to control their blood sugar levels.

“The goal is to correct high glucose levels in real time instead of once a day or twice a day,” Rosenthal says. So far, tests with rats and dogs, spearheaded by Kennedy’s collaborator Sharon F. Grundfest-Broniatowski, a surgeon at the Cleveland Clinic Foundation, have shown preliminary success. Next, the team hopes to do more ad-vanced animal experiments and then move on to human trials.

“If experimental results in vivo show a satisfying survival rate and perfect functions of the macroencapsulated islets, Kennedy’s arti-ficial pancreas will have great potential in clinical applications,” ac-cording to Lina Lu, a doctor in the department of immunology and surgery at the Cleveland Clinic Foundation. —BETHANY HALFORD

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