The body's response to foreign bodies hinders the long-term use of implantable electronic medical devices, such as pacemakers and cochlear implants. Now, in a mouse study, a team led by scientists at the University of Cambridge has shown that this response can be significantly reduced by incorporating an anti-inflammatory drug into the silicone coating around the implant.

"Combining these drugs with different materials and softer device coatings could transform the lives of individuals who need long-term implants to overcome severe disability or disease" - Claire Bryant

Implantable electronic medical devices are already widely used in a variety of applications, but they also offer the prospect of transforming the treatment of difficult-to-treat diseases, such as the use of electrical nerve stimulators in patients with spinal injuries.

However, there is one major problem: Our bodies recognize, attack and wrap these implants with a dense layer of "protective" scar tissue that prevents electrical stimulation from reaching the nervous system.

This so-called "foreign body response" is driven by an inflammatory response to the implant. First, immune cells called macrophages attack and try to destroy the device. A longer-term response then begins, again coordinated by macrophages, which leads to the formation of collagen-rich capsules that separate it from surrounding tissue. This reaction continues until the implant is removed from the body.

The mechanisms by which foreign body reactions occur are poorly understood, meaning there is no effective way to prevent it without interfering with tissue repair mechanisms, such as after nerve injury.

Lead author Dr Damiano Barone, from the University of Cambridge's Department of Clinical Neuroscience, said: "Foreign body reaction is currently an unavoidable implant complication and one of the leading causes of implant failure. Currently, the only way we can prevent it is to use Broad-spectrum anti-inflammatory drugs like dexamethasone. But these are problematic -- they may prevent scarring, but they also prevent repair."

In a study published today in the Proceedings of the National Academy of Sciences (PNAS), scientists implanted an electronic device in mice to compensate for sciatic nerve damage and compared the response in surrounding tissue to those that did not receive the implant. The responses of the mice were compared. In addition to using normal mice, the researchers also used mice in which genes that control the inflammatory response had been "knocked out," preventing the response.

This allowed the team to understand how the body's inflammatory response generates the foreign body response, and which genes are involved. This, in turn, suggests that a specific molecule called NLRP3 plays a key role.

The researchers then added a small molecule called MCC950 to the device coating and tested its effects in mice. MCC950 has previously been shown to inhibit the activity of NLRP3. They found that this prevented the foreign body reaction without affecting tissue regeneration. This is in stark contrast to dexamethasone treatment, which prevents foreign body reactions but also prevents nerve regeneration.

NLRP3 inhibitors are being developed for a variety of clinical applications, including inflammatory diseases, cancer, sepsis, Alzheimer's disease and Parkinson's disease. They are already being tested in clinical trials for certain conditions.

Co-senior author Professor Clare Bryant, from the University of Cambridge's Department of Medicine, said: "This new class of anti-inflammatory drugs is very exciting. Once they pass clinical trials and are proven safe to use, we should be able to integrate them into the next generation of implantable devices. middle.

"Combining these drugs with different materials and softer device coatings could transform the lives of individuals who need long-term implants to overcome severe disabilities or illnesses. In particular, this could potentially have implications for neuroprosthetics (connected to the nervous system) prosthetics), and where these technologies exist, scarring has not yet made their widespread use feasible."