Self-adhesive coatings can prevent scarring around medical implants

When medical devices such as pacemakers are implanted in the body, they usually trigger an immune response that leads to the accumulation of scar tissue around the implant. Scarring, called fibrosis, can interfere with the function of the devices and may require removal.

In developing an advance that could prevent these types of device failures, MIT engineers have found a simple and general way to eliminate fibrosis by coating the devices with a hydrogel adhesive. This adhesive bonds the devices to the tissue and prevents the immune system from attacking them.

“The dream of many research groups and companies is to implant something into the body that the body will not see in the long run, and the device will be able to perform a therapeutic or diagnostic function. Now we have this ‘invisibility cloak,’ and it’s very general: there’s no need for a drug or a special polymer,” says Xuanhe Zhao, a professor of mechanical engineering and civil and environmental engineering at MIT.

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

Zhao and Hyunwoo Yuk SM ’16, PhD ’21, a former MIT scientist and now chief technology officer at SanaHeal, are senior authors of the study, which appears today in the journal Nature. The paper’s lead author is MIT postdoc Jingjing Wu.

Prevention of fibrosis

In recent years, Zhao’s lab 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 tissues using polyacrylic acid, an absorbent material used in diapers. After water is purified, chemical groups called NHS esters embedded in polyacrylic acid form strong bonds with proteins on the tissue surface. This process takes about five seconds.

A few years ago, Zhao and Yuk began investigating whether this type of adhesive could also help keep medical implants in place and prevent fibrosis from occurring.

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

“This work identified a very general strategy, not just for one animal model, one organ, or one application,” Wu says. “In all animal models, we obtained consistent, reproducible results with no noticeable fibrotic capsule.”

Using high-volume RNA sequencing and fluorescence imaging, the researchers analyzed the animals’ immune response and found that when the adhesive-coated devices were first implanted, immune cells such as neutrophils began to infiltrate the area. However, the attacks quickly stopped before any scar could form.

“There is a severe inflammatory reaction with stuck devices because it is a foreign material,” Yuk says. “However, very quickly the inflammatory reaction disappeared and from that point on, fibrosis has not occurred.”

One application of this adhesive could be coatings for epicardial pacemakers – devices placed on the heart to control the heart rate. Wires that come into contact with the heart often become fibrotic, but the MIT team found that after adhesive-coated wires were implanted into rats, they remained functional for at least three months and no scarring formed.

“The formation of fibrotic tissue at the interface between implanted medical devices and the target tissue is a long-term problem that routinely causes device failure. “Demonstrating that strong 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 space,” says David Mooney, a professor of bioengineering at Harvard University who was not involved in the study.

Mechanical tips

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

In another experiment, researchers coated the implants with a hydrogel adhesive and then immersed them in a solution that removed the adhesive properties of the polymers while maintaining their overall chemical structure. After implantation in the body, where they were immobilized with sutures, fibrotic scarring occurred. This suggests that there is something in the mechanical interaction between the adhesive and the tissue that prevents the immune system from attacking it, the researchers say.

“Previous research in immunology has focused on chemistry and biochemistry, but mechanics and physics can play an equivalent role, so we should pay attention to these mechanical and physical signals in immune responses,” says Zhao, who is currently planning further research into how these mechanical signals influence the immune system.

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

“As a team, we’re interested in reporting this to the community and sparking speculation and imagination about where this could go,” Yuk says. “There are many scenarios in which people want to come into contact with foreign or artificial material in the body, such as implantable devices, drug storage facilities, or cell storage facilities.”

Reference: Wu J, Deng J, Theocharidis G, et al. Self-adhesive antifibrotic interfaces on various organs. Nature. 2024. doi: 10.1038/s41586-024-07426-9

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