Adhesive coatings can prevent scarring around medical implants

When medical devices such as pacemakers are implanted in the body, they usually cause an immune response that leads to the build-up of scar tissue around the implant. These scars, known as fibrosis, can interfere with the functioning of the devices and may require their removal.

In a step forward that could prevent these types of device failures, MIT engineers have found a simple and general way to eliminate fibrosis by coating devices with a hydrogel adhesive. This glue binds the devices to the tissue and prevents the immune system from attacking it.

“The dream of many research groups and companies is to implant something into the body that the body will not see in the long term, and the device can provide therapeutic or diagnostic functionality. Now we have such an ‘invisibility cloak’, and this is very general: no drug is needed, no special polymer is needed,” says Xuanhe Zhao, professor of mechanical and civil and environmental engineering at MIT.

The adhesive the researchers used in this study is made of cross-linked polymers called hydrogels and is similar to a surgical tape they previously developed to help seal internal wounds. Other types of hydrogel adhesives can also protect against fibrosis, the researchers found, and they believe this approach could be used not only for pacemakers, but also for sensors or devices that deliver drugs or therapeutic cells.

Zhao and Hyunwoo Yuk SM ’16, PhD ’21, a former MIT researcher and now Chief Technology Officer at SanaHeal, are the senior authors of the study, which appears today in Nature. MIT postdoc Jingjing Wu is the lead author of the paper.

Preventing fibrosis

In recent years, Zhao’s laboratory has developed adhesives for a variety of medical applications, including double-sided and single-sided tapes that can be used to heal surgical incisions or internal injuries. These adhesives work by quickly absorbing water from wet wipes, using polyacrylic acid, an absorbent material used in diapers. Once the water is clear, chemical groups called NHS esters embedded in the polyacrylic acid form strong bonds with proteins on the tissue surface. This process takes about five seconds.

Several years ago, Zhao and Yuk began investigating whether this type of glue could also help keep medical implants in place and prevent fibrosis.

To test this idea, Wu covered polyurethane devices with their glue and implanted them in the abdominal wall, colon, stomach, lungs or heart of rats. Weeks later, they removed the device and discovered that there was no visible scar tissue. Additional tests in other animal models showed the same thing: Wherever the adhesive-coated devices were implanted, fibrosis did not occur, for up to three months.

“This work has really identified a very general strategy, not just for one animal model, one organ or one application,” says Wu. “In all of these animal models, we have consistent, reproducible results without any detectable fibrotic capsule.”

Using bulk RNA sequencing and fluorescent imaging, the researchers analyzed the animals’ immune response and found that when devices with adhesive coatings were first implanted, immune cells such as neutrophils began to infiltrate the area. However, the attacks quickly faded away before scar tissue could form.

“For the attached devices, there is an acute inflammatory response because it involves a foreign material,” says Yuk. “But very quickly that inflammatory response disappeared, and from that moment on you no longer have fibrosis formation.”

One application for this adhesive could be coatings for epicardial pacemakers – devices placed on the heart to help control the heartbeat. The wires that contact the heart often become fibrotic, but the MIT team found that when they implanted glue-coated wires in rats, they remained functional for at least three months, without scar tissue formation.

“The formation of fibrotic tissue at the interface between implanted medical devices and the target tissue is a long-standing problem that routinely causes device failure. The demonstration that robust adhesion between the device and tissue prevents the formation of fibrotic tissue is an important observation that has many potential applications in the medical device field,” said David Mooney, professor of bioengineering at Harvard University, who is not was involved in the research. .

Mechanical signals

The researchers also tested a hydrogel adhesive containing chitosan, a naturally occurring polysaccharide, and found that this adhesive also eliminated fibrosis in animal studies. However, two commercially available tissue adhesives they tested did not show this anti-fibrotic effect, because the commercially available adhesives eventually detached from the tissue and allowed the immune system to attack.

In another experiment, the researchers covered implants with hydrogel adhesives, but then dipped them in a solution that removed the adhesive properties of the polymers while keeping their overall chemical structure the same. After being implanted into the body, where they were held in place by sutures, fibrotic scars formed. This suggests that there is something about the mechanical interaction between the glue and the tissue that prevents the immune system from attacking, the researchers say.

“Previous research in immunology focused on chemistry and biochemistry, but mechanics and physics can play an equal role, and we should pay attention to those mechanical and physical cues in immunological responses,” said Zhao, who now plans to investigate further how those mechanical signals influence the immune system.

Yuk, Zhao and others have started a company called SanaHeal, which is now working to further develop tissue adhesives for medical applications.

“As a team, we are interested in bringing this to the community and encouraging speculation and imagination about where this could go,” says Yuk. “There are so many scenarios where people want to come into contact with foreign or man-made material in the body, such as implantable devices, drug depots or cell depots.”

The research was funded by the National Institutes of Health and the National Science Foundation.

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