Researchers provide better understanding of the body's immune responses to implanted materials

Mar 22 2017

Researchers at MIT and Boston Children's Hospital have published a report today in the journal Nature Materials that provides a better understanding of the body's immune responses to the materials used in implanted medical devices. Funding for this study is made possible through collaboration between JDRF and The Leona M. and Harry B. Helmsley Charitable Trust.

The report, "Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates," could have a significant impact on our future ability to prevent immune rejection of devices that treat type 1 diabetes (T1D), including infusion sets, sensors for continuous glucose monitors (CGMs), and in particular, cell encapsulation and transplantation devices.

"Tens of millions of people in the United States are living with implanted biomedical devices or devices that penetrate the skin. For people with type 1 diabetes, these advances could help improve insulin pump infusion sets, continuous glucose monitors and encapsulation therapies," said Aaron Kowalski, Ph.D., JDRF Chief Mission Officer. "By understanding how to target and prevent unnecessary immune responses to the materials used in medical devices, we can provide therapies that work more effectively and with fewer negative side effects. That would be an incredible step forward in JDRF's mission to cure, prevent and treat T1D."

The study, conducted in rodents and non-human primates, found a significant increase in immune response from colony stimulating factor-1 binding its receptor (CSF1R) following implantation of multiple biomaterial classes such as ceramic, polymer and hydrogel. It also found that specifically targeting CSF1R improved biocompatibility and reduced the thickening and scarring of connective tissue known as fibrosis without the need for broad immunosuppression that would inhibit necessary immune functions like wound healing.

"This gives us a better understanding of the biology behind fibrosis and potentially a way to modulate that response to prevent the formation of scar tissue around implants," said Daniel Anderson, an associate professor in MIT's Department of Chemical Engineering, a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), an affiliate at Boston Children's Hospital, and the senior author of the study.

"One of the things that is particularly exciting to me is that this is one of the first studies to really examine the fundamentals of how the immune system interacts with implantable biomaterials," said Robert Langer, the David H. Koch Institute Professor at MIT and a research associate at Boston Children's Hospital, who was another author of the paper.

Currently, devices like CGMs and infusion sets for insulin pumps must be changed regularly because the body's immune response causes what's known as a fibrotic cascade, preventing the device from interacting with the surrounding microenvironment - making it impossible for the devices to sense glucose levels or effectively deliver insulin. In addition, non-biodegradable microcapsules and macrodevices are being tested to immunoisolate transplanted islet cells in people with T1D, however immune and fibrosis responses directed at the encapsulation material contribute to the failure of the device. Overcoming the rejection of implanted medical devices without the use of broad-spectrum anti-inflammatory drugs could improve the lifespan and effectiveness of the devices, as well as the quality of life for people managing T1D on a daily basis.