Beta cell patch designed to control blood glucose levels

A patch device made of beta cells — the cells that produce insulin — was shown to produce insulin on demand in lab mice induced with diabetes. A team from the biomedical engineering department jointly hosted by University of North Carolina in Chapel Hill and North Carolina State University in Raleigh published its findings earlier this month in the journal Advanced Materials (paid subscription required).

The device is being developed in the labs of biomedical engineering professor Zhen Gu in Raleigh and endocrinologist John Buse in Chapel Hill. The researchers aim to help people with diabetes better control their blood glucose levels with a simple, safe, and inexpensive device. People with diabetes, numbering in the hundreds of millions worldwide and growing, need to measure their blood glucose levels and inject insulin, a process that is often painful and imprecise. In addition, current attempts at closed-loop or self-contained systems use invasive catheters, with mechanical sensors and pumps.

Gu, Buse, and colleagues earlier developed a small square patch device with some 100 hollow microneedles containing biocompatible vesicles, or tiny compartments, filled with insulin. In the presence of glucose, the microneedles oxidize and break open, releasing the insulin into the blood stream. Science & Enterprise reported on this earlier device in June 2015.

The team uses the same physical design for this new patch with tiny hollow microneedles, but instead store natural beta cells in the vesicles instead of insulin. Beta cells usually reside in the pancreas that in healthy people produce insulin. People with type 1 diabetes have an autoimmune condition where the where the body’s defenses attack its own insulin-producing beta cells in the pancreas. In type 2 diabetes, the pancreas produces insulin, but the body does not process that insulin properly, with the pancreas not able to keep blood glucose at normal levels. Some 90 to 95 percent of adults with diabetes have type 2.

Transplants of beta cells so far encountered mixed results, either from immune-system rejection of the transplanted cells, or the need for drugs to suppress the immune system. The Raleigh-Chapel Hill team designed the patch to store beta cells in vesicles made from biocompatible alginate, but the vesicles are sealed preventing beta cells from coming into contact with the blood stream. The microneedles are coated with biocompatible chemicals called glucose-signal amplifiers that react to rising glucose levels.

The patch’s microneedles puncture the outer layers of skin, which causes no pain, but exposes the vesicles to capillaries. When blood glucose levels rise, the glucose-signal amplifiers react, breaking open the vesicles and allowing release of the beta cells into the blood stream, where they produce insulin.

Proof-of-concept tests of the patch using lab mice induced with type 1 diabetes, show the patch quickly responds to high levels of blood glucose, lowers those levels to normal range, and keeps glucose under control for 10 hours. Adding a second patch after that time did not cause blood glucose to fall too low, a condition called hypoglycemia, but maintained glucose at normal levels for another 10 hours.

“This study provides a potential solution for the tough problem of rejection, which has long plagued studies on pancreatic cell transplants for diabetes,” says Gu in a UNC-Chapel Hill statement. “Plus it demonstrates that we can build a bridge between the physiological signals within the body and these therapeutic cells outside the body to keep glucose levels under control.”

The team plans more preclinical testing, and later clinical trials of the patch device.