Implantable devices that release insulin into the body hold promise as an alternative way
to treat diabetes without insulin injections or cannula insertions.
However, one obstacle that has prevented their use so far 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.
However, a team of MIT engineers and collaborators has now devised a way to overcome this response.
In a study of mice, they 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.
Among other possible applications, the researchers now plan to see if they can use the device
to deliver pancreatic islet cells that could act as an “bioartificial pancreas” to
help treat diabetes.
Most patients with type 1 diabetes, and some with type 2 diabetes, have to inject themselves
with insulin on a daily basis.
Some patients use wearable insulin pumps that are attached to the skin and deliver insulin
through a tube inserted under the skin, or patches that can deliver insulin without a
tube.
For many years, scientists have been working on insulin-delivering devices that could be
implanted under the skin.
However, the fibrous capsules that form around such devices can lead to device failure within
weeks or months.
Researchers have tried many approaches to prevent this kind of scar tissue from forming,
including local delivery of immunosuppressants.
The MIT team took a different approach that does not require any drugs — instead, their
implant includes a mechanically actuated soft robotic device that can be inflated and deflated.
In a 2019 study, the researchers showed that this kind of oscillation can modulate how
nearby immune cells respond to an implanted device.
In the new study, the researchers wanted to see if that immunomodulatory effect could
help improve drug delivery.
They built a two-chambered device made of polyurethane, a plastic that has 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, the researchers can stimulate the actuator to inflate and
deflate on a specific schedule.
For this study, they performed the actuation every 12 hours, for five minutes at a time.
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
fibers that built up around static devices, collagen fibers surrounding actuated devices
were more highly aligned, which the researchers believe may help drug molecules to pass through
the tissue.
To demonstrate the potential usefulness of this device, the researchers showed that it
could be used to deliver insulin in mice.
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.
The researchers evaluated the effectiveness of the insulin release by measuring subsequent
changes in the mice’s blood glucose levels.
They found that in mice with the actuated device, effective insulin delivery was maintained
throughout the eight weeks of the study.
However, in mice that did not receive actuation, delivery efficiency began to wane after only
two weeks, and after eight weeks, almost no insulin was able to pass through the fibrous
capsule.
The authors also created a human-sized version of the device, 120 millimeters by 80 millimeters,
and showed that it could be successfully implanted in the abdomen of a human cadaver.
This was a proof of concept to show that there is a minimally invasive surgical technique
that could potentially be employed for a larger-scale, human-scale device.
Working with Jeffrey Millman of the Washington University School of Medicine in St. Louis,
the researchers now plan 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.
Such an implant could eliminate the need for patients to constantly measure their glucose
levels and inject insulin.
Other possible applications the researchers have explored for this kind of device 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.