From pacemakers to drug delivery systems, implantable medical devices have improved millions of lives worldwide. Yet despite their benefits, they face a persistent hurdle – foreign body reactions, in particular scar tissue formation around the device. When the immune system detects a foreign object, the resulting scar tissue produced (known as a fibrous capsule) can lead to implant failure and put patients at risk. However, researchers are exploring innovative adhesives to tackle the problem, which could enhance the longevity and reliability of medical implants.
“Fibrous capsule formation around implants is a big problem,” says mechanical engineer Xuanhe Zhao from the Massachusetts Institute of Technology in Boston, US. “It is ubiquitous around devices in the body, causing a significant portion of implant failures.” This often necessitates additional surgeries, prolongs patient recovery, and, in severe cases, leads to the failure of life-saving devices. These complications also drive up healthcare costs due to additional time-intensive procedures and resource demands. For example, severe fibrous capsule formation around breast implants can cause discomfort, pain and distortion of the implant’s shape, sometimes requiring surgical removal or replacement. In 2020, more than 58,000 breast implant reoperations were done in the US due to the scar tissue becoming hard and starting to contract, reports a 2021 paper in the journal Cells.
Similarly, scarring around drug delivery implants reduces the medicine’s efficacy. In pacemakers or other cardiac devices, fibrous capsules can obstruct the function of pacing leads, potentially causing device failure, Zhao adds. With his team’s adhesive, Zhao hopes to overcome these problems, so implants can do their job without inciting the immune system.
Immune attack
Preventing scar tissue formation isn’t easy. The body’s immune system is a double-edged sword. It might protect us from harmful invaders, but it can also overreact to interventions designed to improve health. When an implant is inserted into the body, the immune system marks it out as a foreign object. This triggers an inflammatory response and the body can then begin to encapsulate the implant with a layer of fibrous tissue, in an attempt to isolate it from the surrounding tissue. But what if the implant could bind straight to those surrounding tissues, preventing scar tissue from forming?
That’s the thinking behind the MIT team’s approach. Biomedical engineers have been trying to address the problem of fibrous capsule formation for many years, says Zhao. But in 2019, his team made a nature-inspired breakthrough, originally developed to help seal wounds.
Designing an adhesive to stick two dry surfaces together is relatively straightforward, thanks to forces like hydrogen bonds and electrostatic interactions. However, achieving this kind of instant adhesion is much harder with wet surfaces, such as body tissues. The water between the surfaces acts as a barrier, stopping the molecules from connecting. So while tissue adhesives have many potential benefits (such as reducing pain and faster application) over traditional methods like sutures or staples for sealing wounds, the options we currently have often fall short. Animals like mussels, barnacles and spiders have developed natural adhesives that work effectively in wet environments. These creatures use mechanisms to actively push away water from surfaces, enabling strong bonds to form. Inspired by these natural strategies, the MIT team designed a dry-crosslinking adhesive to mimic the approach. It removes water from wet tissues at the interface, allowing a secure bond to form even in moist conditions. The MIT hydrogel adhesive rapidly absorbs fluid from body tissues using polyacrylic acid, an absorbent material used in nappies. Once the water is cleared, chemical groups called NHS esters from the acid form strong bonds with proteins at the tissue surface in a matter of seconds.
Double and single-sided tapes made with this bioadhesive were initially intended for surgical incisions and internal injuries. However, Zhao and his colleagues were curious about how it could be applied to implants. “I wondered whether the conformal and robust adhesion could prevent fibrosis on the implant-tissue interfaces,” Zhao explains. The team’s research changed direction – they began to apply the bioadhesive to medical implants to see if it could mitigate fibrous capsule formation. The team’s adhesive employs a dual strategy to stop scarring in its tracks, Zhao reveals.
Double action
For one, the MIT hydrogel prevents scar tissue formation by reducing protein absorption on the implant’s surface. Additionally, micromotion – tiny movements between the implant and surrounding tissue – can activate inflammation and scarring. The MIT hydrogel forms a tight bond with tissues, stabilising the interface and minimising mechanical forces that could provoke an immune response. “The adhesion reduces and delays protein absorption on the interfaces and prevents any relative micromotion between the implant and the tissue,” Zhao explains. “Overall, this dramatically reduces immune cell infiltration to the interfaces.”
Zhao’s team demonstrated the hydrogel’s effectiveness in animal models, as detailed in a study published in Nature in June 2024. Coating polyurethane devices with the adhesive, the scientists implanted them onto the abdominal wall, colon, stomach, lung or heart of rats. Weeks later, the devices were removed with no visible scar tissue. Tests in other animals, including humanised mice and pigs, yielded similar results: no fibrosis for the three-month experiment.
To analyse the animals’ immune response, the researchers used bulk RNA sequencing and fluorescent imaging. Results showed that when devices with the MIT adhesive coating were first implanted, immune cells did begin to infiltrate the area. But the immune attack was quickly quelled before any scar tissue formed.
“This work really has identified a very general strategy, not only for one animal model, one organ or one application,” said MIT postdoc Jingjing Wu and lead author of the Nature paper in an accompanying press release. “Across all of these animal models, we have consistent, reproducible results without any observable fibrotic capsule.”
In another experiment, the researchers coated implants with the same hydrogel treated with a solution that neutralised its adhesive properties while preserving its overall chemical composition. Once implanted in the body and secured with sutures, these modified implants did trigger fibrotic scarring. According to the researchers, this finding suggests that the adhesive’s mechanical interaction with the tissue plays a critical role in preventing the immune system from initiating an inflammatory response. The team also tested a hydrogel adhesive that included chitosan, a naturally occurring sugar, which similarly eliminated fibrosis in animal studies. Two commercially available tissue adhesives were tested as well, but they failed to mount an antifibrotic effect, eventually detaching from the tissue and allowing the immune system to attack.
A universal approach
Traditional approaches to mitigating fibrous capsule formation often rely on surface modifications or drugeluting coatings, says Zhao. But this dependence on specific substances can be a limitation, given that we need solutions for a wide variety of medical devices that are made from diverse materials.
On the other hand, hydrogel adhesive can be used with any material and is drug free, meaning it can be applied to implants of any material – be it metal, plastic or silicone. This universality represents a significant leap forward, as it simplifies the process of creating and applying implant coatings. For instance, there’s no need for complex formulations or tailored approaches – you just use the adhesive. “I was so surprised to see the broad applicability of the adhesive non-fibrotic interface on diverse organs [and] in various animal models,” says Zhao. One potential application is as a coating for epicardial pacemakers, devices attached directly to the heart to regulate its rhythm. The wires connecting these to the heart often become encased in fibrotic tissue, which can impair their function. However, the MIT team demonstrated that when adhesive-coated wires were implanted in rats, they remained fully operational for at least three months without evidence of scar tissue formation. The adhesive has only been tested in animal models, so clinical research is needed before it can be deemed safe for humans. But Zhao’s team are working on it: they’re currently studying more detailed interactions between the hydrogel adhesive and the immune system, while exploring additional applications. To accelerate commercialisation, the MIT researchers founded SanaHeal, a startup pursuing clinical trials and FDA approval for products based on this bioadhesive technology.
It’s the dream of many research groups and companies to create an implant that, over the long term, the body doesn’t ‘see’ yet that still does what it’s supposed to, whether that’s to diagnose or deliver therapy, says Zhao. “Now we have such an ‘invisibility cloak’… There’s no need for a drug, no need for a special polymer.”
