Device could pave way for new diabetes treatment

Implantable devices that release insulin into the body could provide an alternative diabetes treatment to insulin injections or cannula insertions. However, an obstacle that has prevented their use is that the immune system attacks them after implantation, forming a thick layer of scar tissue that blocks insulin release.

This phenomenon, known as the foreign body response, can also interfere with many other types of implantable medical devices. The team at MIT has now devised a way to overcome this response.

In a study of mice, researchers showed that when they incorporated mechanical actuation into a soft robotic device, the device remained functional for much longer than a typical drug-delivery implant. 

The device is repeatedly inflated and deflated for five minutes every 12 hours, and this mechanical deflection prevents immune cells from accumulating around the device, researchers found.

“We’re using this type of motion to extend the lifetime and the efficacy of these implanted reservoirs that can deliver drugs like insulin, and we think this platform can be extended beyond this application,” said Ellen Roche, the Latham Family Career Development associate professor of Mechanical Engineering and a member of MIT’s Institute for Medical Engineering and Science.

Among other applications, the team now plans to see if the device can be used to deliver pancreatic islet cells that could act as a ‘bioartificial pancreas’ to treat diabetes.

Scientists have been working on implantable insulin-delivering devices for years, researchers said, but the fibrous capsules that form around such devices can lead to device failure within weeks or months. Local delivery of immunosuppressants has been explored to prevent scar tissue forming, but the MIT team’s soft robotic approach does not require any drugs. In a 2019 study, Roche and her colleagues showed how the oscillation can modulate nearby immune cells’ response.

In the new study, researchers wanted to see if the immunomodulatory effect could improve drug delivery. They built a two-chambered device made of polyurethane, a plastic with similar elasticity to the extracellular matrix that surrounds tissues. One of the chambers acts as a drug reservoir, and the other acts as a soft, inflatable actuator. Using an external controller, they can simulate the actuator to inflate and deflate on a specific schedule. 

This mechanical actuation drives away immune cells called neutrophils, the cells that initiate the process that leads to scar tissue formation. When the researchers implanted these devices in mice, they found that it took much longer for scar tissue to develop around the devices. Scar tissue did eventually form, but its structure was unusual: instead of the tangled collagen fibres that built up around static devices, collagen fibres surrounding actuated devices were more highly aligned, which researchers believe may help drug molecules to pass through the tissue.

The device is designed so that insulin can slowly seep out through pores in the drug reservoir or be released in a large burst controlled by the actuator.

When measuring changes in the mice’s blood glucose levels, they found that in mice with the actuated device, effective insulin delivery was maintained over eight weeks. However, in mice that didn’t receive actuation, delivery efficiency began to wane after only two weeks, and after eight weeks, no insulin was able to pass through the fibrous capsule.

The authors also created a human-sized version of the device, 120mm x 80mm, and showed that it could be successfully implanted in the abdomen of a human cadaver.

Working with Jeffrey Millman of the Washington University School of Medicine in St. Louis, the team now plans to adapt the device so that it could be used to deliver stem-cell-derived pancreatic cells that would sense glucose levels and secrete insulin when glucose is too high. This could eliminate the need for patients to constantly measure their glucose levels and inject insulin.

Other possible applications include delivery of immunotherapy to treat ovarian cancer, and delivering drugs to the heart to prevent heart failure in patients who have had heart attacks.

The research was funded, in part, by Science Foundation Ireland, the Juvenile Diabetes Research Foundation, and the National Institutes of Health.