Working Closer and Closer to a Cure?

I have never been more proud of my Alma Mater - The University of Akron- and some of the amazing diabetes research they are currently working on. They give HOPE to all of us that one day a CURE will be found.

Perfecting An Artifical Pancreas:
specialized polymer is key to insulin-regulating device

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 ravages 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 pancreas. He spoke about its construction during 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 million people worldwide have diabetes, 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 pancreas technologies. Most strategies involve transplanting healthy islets—the pancreatic cells that detect 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 approach. 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 hexagonal holes. Polyurethane nanofibers are then electrospun over the tube, through techniques designed by Kennedy's colleague Miko Cakmak, who is a polymer engineering professor at Akron. The resulting entanglement of nanofibers, or so-called nanomats, reinforces the openings in the scaffold's mesh.

THE TUBE is then coated with a semipermeable polymer membrane made up of poly(dimethylacrylamide) and polydimethylsiloxane domains cross-linked by polymethylhydrosiloxane. The entire 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 membrane is really what sets this artificial pancreas apart. Encapsulating a large collection of islets has been difficult, he says, because the material 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 attack 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 molecules 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 biocompatible, flexible, transparent, autoclavable, and they're easily synthesized 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 background 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 precisely 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 advanced 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 artificial pancreas will have great potential in clinical applications," according to Lina Lu, a doctor in the department of immunology and surgery at the Cleveland Clinic Foundation.

Color-changing contact lenses to help diabetics

FOR THE MILLIONS of Americans with diabetes, the inconvenient and often painful method of testing blood sugar levels is a way of life. But research and innovative product design by scientists at The University of Akron may eliminate the need for needle pricks, blood draws, or other invasive devices.

Researchers have developed a contact lens that senses glucose which is the blood sugar in tears, the natural fluid that bathes the eye. If sugar is not being metabolized properly and glucose concentration builds up in the body, the contact lens will detect a problem and change color.

“It works just like pH paper in your high school chemistry lab,” explains Dr. Jun Hu, associate professor of chemistry at The University of Akron. “The pH paper changes color depending on the acidity or the proton concentration of the liquid applied. That is similar to what happens in our specially designed contact lens, the sugar molecule literally acting like the proton in a pH test, displacing a color dye embedded in the lens, and the lens changes color.

”The person wearing the lens won’t notice the color change unless he or she looks in the mirror. So scientists are designing a smart phone application (“app”) that literally takes a picture of the eye and calculates the sugar concentration in the lens. “All you need is a smart phone with a camera,” says Dr. Hu, an organic chemistry researcher who has been with UA since 1999. “This device could be used to detect subtle changes in blood sugar levels for tight management of diabetes. It can also be used to identify patients with pre-diabetic conditions, allowing early diagnosis that is crucial for preventing diabetes from advancing. Glucose concentrations in tears can be used to intermittently or continuously monitor diabetic patients just as effectively as blood sugar levels measured directly from blood from a pricked finger.

”The convenience of contact lenses could boost patient compliance to blood sugar testing, as it will reduce discomfort, inconvenience, and even cost. In addition, blood sugar also changes rapidly throughout a normal, active day, so a device that can monitor glucose many times in a day will provide diabetic patients with a very powerful tool in combating such a damaging condition.