Synthetic materials such as silicone are widely used in medical implants, but they can trigger an immune response that leads to harmful scarring. Now, a new study in the April 15 issue of Science Translational Medicine reveals how immune cells form lumps of connective tissue around synthetic materials in breast implants.
The results — gathered from mouse studies and an analysis of breast implants from 12 patients — may provide new treatment strategies for researchers aiming to dampen the immune system's response to implants.
Synthetic materials, including silicone and polycaprolactone, are major components of medical devices and prosthetics such as reconstructive breast implants and tracheal stents. Historically, researchers have used materials that have favorable physical properties and durability while inciting the smallest possible response from the immune system, according to the study.
However, even the best synthetic materials still generate an aggressive response from the immune system — termed a foreign body response. In this phenomenon, the body forms high amounts of scar tissue around the implant, according to Jennifer Elisseeff, professor of biomedical engineering at the Johns Hopkins University School of Medicine and senior author of the new study.
The foreign body response is one reason that many implants degenerate and fail over time, she said. Damaged implants require the patient to undergo additional surgical procedures, raising the risk of complications such as bleeding and infections.
Furthermore, some studies link the foreign body response to other complications such as lymphoma and breast implant syndrome, which causes debilitating symptoms like breast pain and can heighten the risk of diseases like rheumatoid arthritis.
Together, these risks and complications pose a major obstacle to women receiving breast implants for cosmetic or reconstructive purposes. Researchers have therefore begun to investigate whether there might be biological pathways that could be targeted with drugs to dissuade the immune system from forming too much scar tissue around implants.
"The problem with scar formation around implants has been longstanding," said Elisseeff. "If we can better integrate devices and implants we can increase the lifetime and performance of the implants."
To better understand the origins of the foreign body response, Liam Chung, a postdoctoral researcher at Johns Hopkins University and lead author of the new study, and colleagues studied the capsules of scar tissue surrounding silicone breast implants that had been surgically removed from 12 women.
They discovered that the formation of fibrotic scar tissue was largely due to the activity of an immune molecule named IL-17. This molecule was secreted by various T cells, including an unconventional type called gamma-delta T cells that can recognize a wide variety of foreign molecules.
The scientists also observed higher numbers of stromal cells — which support the function of organs — in a senescent or dormant state in the surrounding tissue.
"[Senescent] cells are primarily studied in the context of aging and had never before been studied in biomaterial responses," said Elisseeff. "This [discovery] also allowed us to make a connection between IL-17 and senescence that is new."
The researchers then investigated whether targeting IL-17 could have therapeutic effects in mice implanted with polycaprolactone and other types of synthetic materials.
The results showed that blocking IL-17 with an antibody injection lowered the formation of harmful scar tissue in the animals. Killing senescent cells with the experimental drug navitoclax had a similar effect, suggesting that either treatment strategy could potentially mitigate fibrosis and other complications linked to synthetic implants.
The researchers cautioned the mouse models included in the research don't fully represent the impact of implanting synthetic devices in people, meaning more trials are needed to see whether an IL-17-blocking treatment would work in the clinic.
The scientists also call for additional studies to more fully explain why the body's T cells end up supporting pro-fibrosis pathways, as well as to flesh out the IL-17 immune response in other types of synthetic materials and medical implants.
"From the basic research side we are studying the gamma delta cells in more detail and also trying to understand more about the senescent cells," said Elisseeff. "Therapeutically, we are looking at inhibitors of IL17 and senescent cells … for reducing this fibrosis."