Engineers have discovered a method to stop the development of scar tissue around implantable devices. By applying a hydrogel adhesive coating to the devices, the material connects the device to the tissue and prevents the immune system from rejecting it. When medical devices such as pacemakers are inserted into the body, they typically trigger an immune response that results in the formation of scar tissue around the implant. This scarring, also known as fibrosis, can disrupt the operation of the devices and may necessitate their removal. This breakthrough from MIT engineers could potentially prevent such device malfunctions.Researchers have discovered a straightforward method to prevent fibrosis by using a hydrogel adhesive to coat devices. This adhesive allows the devices to bond with tissue and protects them from the body’s immune response.
“Many research groups and companies have longed to implant something in the body that remains undetected by the body over time, and which can deliver therapeutic or diagnostic benefits. Now we have such an ‘invisibility cloak,’ and it is very versatile: No medication or special polymer is required,” explains Xuanhe Zhao, an MIT professor of mechanical engineering and civil and environmental engineering.
TheThe adhesive used in the study is made from hydrogels, which are cross-linked polymers. It is similar to a surgical tape developed by the researchers to seal internal wounds. The researchers discovered that other types of hydrogel adhesives can also protect against fibrosis. They believe that this approach can be used for pacemakers, sensors, or drug and therapeutic cell delivery devices. Senior authors of the study include Zhao and Hyunwoo Yuk SM ’16, PhD ’21, who is now the chief technology officer at SanaHeal. The study will be published in Nature. Jingjing Wu, a postdoc at MIT, also contributed to the study.Zhao is the primary author of the article.
“Preventing fibrosis”
Zhao’s laboratory has created adhesives for various medical purposes in recent times, such as double-sided and single-sided tapes that have the potential to heal surgical incisions or internal injuries. These adhesives function by quickly absorbing moisture from wet tissues, utilizing polyacrylic acid, a material known for its absorbent properties in diapers. Once the moisture is absorbed, chemical groups known as NHS esters that are part of the polyacrylic acid create strong bonds with proteins on the surface of the tissue. This entire process happens within approximately five seconds.Several years ago, Zhao and Yuk started to investigate if this type of adhesive could also be used to secure medical implants and prevent fibrosis. Wu conducted experiments by applying the adhesive to polyurethane devices and implanting them in various parts of rats’ bodies. After removing the devices weeks later, they observed no visible scar tissue. Further tests on other animals showed the same result: fibrosis did not occur for up to three months in areas where the adhesive-coated devices were implanted. This research has discovered a broad approach for preventing fibrosis.According to Wu, regardless of the animal model, organ, or application, consistent and reproducible results were obtained without any visible fibrotic capsule. The researchers used bulk RNA sequencing and fluorescent imaging to analyze the animals’ immune response and discovered that when devices with adhesive coatings were initially implanted, immune cells such as neutrophils infiltrated the area. However, the attacks were quickly extinguished before any scar tissue could develop. Yuk added that adhered devices elicited an acute inflammatory response due to being a foreign material, but this response quickly subsided.The inflammation response decreased, preventing the formation of fibrosis. The adhesive can potentially be used for coating epicardial pacemakers, which are devices placed on the heart to regulate the heart rate. The MIT team discovered that when they implanted adhesive-coated wires in rats, the wires remained functional for at least three months without forming scar tissue, preventing fibrosis. The researchers also experimented with a hydrogel adhesive containing chitosan, a naturally occurring polymer.The researchers conducted experiments with a type of adhesive called polysaccharide, and discovered that it not only stuck to tissue, but also prevented fibrosis in animals. However, when they tested two tissue adhesives that are commercially available, they did not have the same antifibrotic effect. This was because these adhesives eventually detached from the tissue, allowing the immune system to attack.
In another experiment, the researchers coated implants with hydrogel adhesives, and then soaked them in a solution that removed the adhesive properties of the polymers, while keeping their chemical structure intact. When implanted in the body and held in place by sutures, fibrotic scarring occurred.The researchers suggest that the way the adhesive interacts with the tissue may prevent the immune system from attacking it. According to Zhao, previous research has mainly focused on chemistry and biochemistry in immunology, but the role of mechanics and physics should not be overlooked. He plans to investigate further how these mechanical cues affect the immune system. Zhao, Yuk, and others have founded a company called SanaHeal, which is focused on advancing tissue adhesives for medical use.The team is eager to share their findings with the community and inspire speculation and curiosity about the potential applications of their research. There are numerous scenarios in which people may want to interact with foreign or man-made materials in the body, such as implantable devices, drug depots, or cell depots. The research received funding from the National Institutes of Health and the National Science Foundation.
