Implantable devices that release insulin in to the body hold promise alternatively solution to treat diabetes without insulin injections or cannula insertions. However, one obstacle which has prevented their use up to now is that the disease fighting capability attacks them after implantation, forming a thick layer of scar tissue formation that blocks insulin release.
This phenomenon, referred to as the foreign body response, may also interfere with a great many other forms of implantable medical devices. However, a team of MIT engineers and collaborators has devised a method to overcome this response. In a report of mice, they showed that whenever they incorporated mechanical actuation right into a soft robotic device, these devices remained functional for a lot longer when compared to a typical drug-delivery implant.
These devices is repeatedly inflated and deflated for 5 minutes every 12 hours, which mechanical deflection prevents immune cells from accumulating round the device, the researchers found.
“We’re using this motion to increase the lifetime and the efficacy of the implanted reservoirs that may deliver drugs like insulin, and we think this platform could be extended beyond this application,” says Ellen Roche, the Latham Family Career Development Associate Professor of Mechanical Engineering and an associate of MIT’s Institute for Medical Engineering and Science.
Among other possible applications, the researchers now intend to see should they can use these devices to provide pancreatic islet cells which could become an “bioartificial pancreas” to greatly help treat diabetes.
Roche may be the co-senior writer of the analysis, with Eimear Dolan, a former postdoc in her lab who’s now a faculty member at the National University of Ireland at Galway. Garry Duffy, also a professor at NUI Galway, is really a key collaborator on the task, which appears in Nature Communications. MIT postdocs William Whyte and Debkalpa Goswami, and visiting scholar Sophie Wang, will be the lead authors of the paper.
Modulating immune cells
Most patients with type 1 diabetes, plus some with type 2 diabetes, need to inject themselves with insulin every day. Some patients use wearable insulin pumps which are attached to your skin and deliver insulin by way of a tube inserted beneath the skin, or patches that may deliver insulin with out a tube.
For several years, scientists have already been focusing on insulin-delivering devices that may be implanted beneath the skin. However, the fibrous capsules that form around such devices can result in device failure within weeks or months.
Researchers have tried many methods to prevent this type of scar tissue formation from forming, including local delivery of immunosuppressants. The MIT team took another approach that will not require any drugsinstead, their implant carries a mechanically actuated soft robotic device which can be inflated and deflated. In a 2019 study, Roche and her colleagues (with Dolan as first author) showed that sort of oscillation can modulate how nearby immune cells react to an implanted device.
In the brand new study, the researchers wished to see if that immunomodulatory effect may help improve drug delivery. They built a two-chambered device manufactured from polyurethane, a plastic which has similar elasticity to the extracellular matrix that surrounds tissues. Among the chambers acts as a drug reservoir, and another acts as a soft, inflatable actuator. Utilizing an external controller, the researchers can stimulate the actuator to inflate and deflate on a particular schedule. Because of this study, they performed the actuation every 12 hours, for 5 minutes at the same time.
This mechanical actuation drives away immune cells called neutrophils, the cells that initiate the procedure leading to scar tissue formation formation. Once the researchers implanted the unit in mice, they discovered that it took a lot longer for scar tissue formation to develop round the devices. Scar tissue formation did eventually form, but its structure was unusual: Rather than the tangled collagen fibers that developed around static devices, collagen fibers surrounding actuated devices were more highly aligned, that your researchers believe can help drug molecules to feed the tissue.
“For a while, we see there are fewer neutrophils surrounding these devices in the tissue, and longterm, we see there are differences in collagen architecture, which might be linked to why we’ve better drug delivery through the entire eight-week time frame,” Wang says.
Sustained drug delivery
To show the potential usefulness of the device, the researchers showed that maybe it’s used to provide insulin in mice. These devices is designed in order that insulin can slowly seep out through pores in the drug reservoir or be released in a big burst controlled by the actuator.
The researchers evaluated the potency of the insulin release by measuring subsequent changes in the mice’s blood sugar levels. They discovered that in mice with the actuated device, effective insulin delivery was maintained through the entire eight weeks of the analysis. However, in mice that didn’t receive actuation, delivery efficiency started to wane after only fourteen days, and after eight weeks, minimal insulin could go through the fibrous capsule.
The authors also created a human-sized version of these devices, 120 millimeters by 80 millimeters, and showed that maybe it’s successfully implanted in the abdomen of a human cadaver.
“This is a proof concept showing that there surely is a minimally invasive surgical technique which could potentially be used for a larger-scale, human-scale device,” Goswami says.
Dealing with Jeffrey Millman of the Washington University School of Medicine in St. Louis, the researchers now intend to adapt these devices in order that it could possibly be used to provide stem-cell-derived pancreatic cells that could sense sugar levels and secrete insulin when glucose is too much. This implant could get rid of the dependence on patients to constantly measure their sugar levels and inject insulin.
“The theory will be that the cells will be resident in the reservoir, plus they would become an insulin factory,” Roche says. “They might detect the degrees of glucose in blood and release insulin in accordance with that which was necessary.”
Other possible applications the researchers have explored because of this sort of device include delivery of immunotherapy to take care of ovarian cancer, and delivering drugs to the center to avoid heart failure in patients who’ve had heart attacks.
“Imaginable that people can apply this technology to whatever is hindered by way of a foreign body response or fibrous capsule, and also have a long-term effect,” Roche says. “I believe any kind of implantable drug delivery device could benefit.”
More info: William Whyte et al, Dynamic actuation enhances transport and extends therapeutic lifespan within an implantable drug delivery platform, Nature Communications (2022). DOI: 10.1038/s41467-022-32147-w
Citation: Design prevents buildup of scar tissue formation around medical implants (2022, August 5) retrieved 7 August 2022 from https://medicalxpress.com/news/2022-08-buildup-scar-tissue-medical-implants.html
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