Incorporating anti-inflammatory medications into the coating of implants to reduce reactional effects

Incorporating anti-inflammatory medications into the coating of implants to reduce reactional effect ...

The body''s reaction to foreign bodies has hampered the long-term use of implantable electronic medicines such as pacemakers and cochlear implants. Currently, a team led by scientists at the University of Cambridge has shown that this reaction can be significantly reduced by using a novel anti-inflammatory medication in the silicone coating around the implant.

Implantable electronic medical devices are already widely used for a range of applications, but they also offer the prospect of revolutionizing the treatment of difficult situations, such as the use of neural electrical stimulation for spinal injury patients.

However, there is one major issue: our body recognizes, attacks, and surrounds these implants with a dense, protective capsule of scar tissue that prevents electrical stimulation reaching the nervous system.

This so-called foreign body reaction is influenced by an inflammatory response against the implant. First, immune cells known as macrophages attack and attempt to destroy the device. Then a more long-term response starts in, coordinated by macrophages, which leads to the build-up of a collagen-rich capsule to isolate it from the surrounding tissue. This response then persists until the implant is removed from the body.

The mechanisms by which an external body reaction occurs are poorly understood, meaning that there are no effective methods to prevent it without involving tissue repair techniques, for example after nerve damage.

Dr Damiano Barone of the University of Cambridge''s Clinical Neurosciences said that foreign body reaction is currently an unavoidable result of implantation and is one of the leading causes of implant failure. At the moment, the only way we can get rid of it is to use broad-spectrum anti-inflammatory medications such as dexamethasone. These are however problematic, they may cure the scarring, but they also stop the repair.

Researchers applied an electrical device to mice to help compensate for sciatic nerve damage, compared the response within the surrounding tissue to those who did not receive an implant. In a research published today in theProceedings of the National Academy of Sciences (PNAS), scientists found that the genes controlling the inflammatory response had been knocked out, preventing a response.

This enabled the team to see how the body''s inflammatory response created the foreign body reaction, and which genes were involved. In turn, this showed that a particular substance known as NLRP3 plays a key role.

The researchers added a small molecule known as MCC950 to the device coating and examined the effect in mice. MCC950 has previously been shown to inhibit the activity of NLRP3. This altered tissue regeneration, which is contrasted with a dexamethasone therapy, which prevents the foreign body reaction but also blocks nerve regeneration.

NLRP3 inhibitors are currently being developed for a wide spectrum of clinical applications, including inflammatory disease, cancer, sepsis, Alzheimers disease, and Parkinsons disease. They are already being tested in clinical trials for certain conditions.

Professor Clare Bryant, a joint senior author, believes this new class of anti-inflammatory drugs is growing. Once they have been successfully evaluated and tested to be safe to use, we should be in a position to incorporate them into the next generation of implantable devices.

Combining these medications with different materials and lessen coatings for devices might alter the lives of individuals who need long-term implants to overcome serious illness or illness. In particular, this might make a huge difference to neuroprosthetics prosthetics that connect to the nervous system where the technology exists, but scarring has not yet made their widespread use viable.

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