New sprayable gel promises safer endoscopic procedures

More than 20 million Americans undergo colonoscopy screenings each year, and in many of these cases, doctors end up removing polyps that are 2 cm or larger and require additional care. This procedure has significantly reduced the overall incidence of colon cancer, but not without complications, as patients can experience gastrointestinal bleeding both during and after the procedure.

Hoping to prevent these complications, researchers at MIT have developed a new gel, GastroShield, that can be sprayed into surgical sites through an endoscope. This gel forms a tough yet flexible protective layer that serves as a shield for the damaged area. The material prevents delayed bleeding and enhances the mechanical integrity of the tissue.

Tissue-responsive adhesive technology is designed to interact with tissue through complementary covalent and ionic interactions as well as physical interactions to provide prolonged damage protection for days to prevent complications after removal of polyps and other bleeding-risk wounds in gastrointestinal tract. “

Natalie Artzi, principal investigator at MIT’s Institute for Medical Engineering and Science, associate professor of medicine at Harvard Medical School, and senior author of the paper

In an animal study, researchers showed that the GastroShield application integrates seamlessly with current endoscopic procedures and provides wound protection for three to seven days, where it helps tissue heal after surgery. Artzi and other members of the research team have started a company called BioDevek that now plans to further develop the material for use in humans.

Gonzalo Muñoz Taboada, CEO of BioDevek, and Daniel Dahis, Chief Scientist at BioDevek, are lead authors of the study, which is published in the journal Advanced Materials. Elazer Edelman, the Edward J. Poitras Professor in Medical Engineering and Science at MIT and director of IMES, and Pere Dosta, a former postdoctoral fellow in Artzi’s lab, are also authors of the paper.

Adhesive gels

Routine colon cancer screenings often reveal small precancerous polyps, which can be removed before they become cancerous. This is usually done using an endoscope. If any bleeding occurs during polyp removal, doctors can cauterize the wound to seal it, but this method creates a scar that can delay healing and lead to additional complications.

In addition, in some patients, bleeding does not occur until a few days after the procedure. This can be dangerous and may require patients to return to the hospital for additional treatment. Other patients may develop small tears that cause intestinal contents to leak into the abdomen, which can lead to serious infection and require emergency care.

When tissue reinforcement is required, doctors often insert metal clips to hold the tissue together, but these cannot be used with larger polyps and are not always effective. Attempts to develop a gel that could seal surgical wounds were unsuccessful, primarily because the materials could not adhere to the surgical site for more than 24 hours.

The MIT team looked at dozens of combinations of materials they thought might have the right properties for this use. They wanted to find formulations that would exhibit a low enough viscosity to be easily administered and sprayed through a nozzle at the end of a catheter that fits inside commercial endoscopes. At the same time, upon contact with the tissue, this formulation should immediately form a hard gel that adheres strongly to the tissue. They also wanted the gel to be flexible enough to withstand the forces created by the peristaltic movements of the digestive tract and the food flowing through it.

The researchers came up with a winning combination that includes a polymer called pluronic, which is a type of block copolymer that can self-assemble into spheres called micelles. The ends of these polymers contain multiple amine groups, which terminate on the surface of the micelles. The second component of the gel is oxidized dextran, a polysaccharide that can form strong but reversible bonds with the amine groups of pluronic micelles.

When sprayed, these materials immediately react with each other and with the lining of the gastrointestinal tract, forming a solid gel in less than five seconds. The micelles that make up the gel are “self-healing” and can absorb the forces they encounter from peristaltic movements and food moving along the digestive tract, by temporarily breaking down and then reassembling.

“To obtain a material that complies with the design criteria and can be delivered through existing colonoscopes, we screened through material libraries to understand how different parameters affect gelation, adhesion, retention and compatibility,” says Artzi.

Protective layer

The gel can also withstand the low pH and enzyme activity in the digestive tract and protect tissue from this harsh environment while it self-heals, highlighting its potential for use in other gastrointestinal wounds with a high risk of bleeding, such as stomach ulcers, which affect more by 4 million Americans each year.

In animal tests, the researchers found that every animal treated with the new gel experienced rapid sealing and no perforations, leaks or bleeding in the week following treatment. The material lasted for about five days, after which it was removed along with the top layer of tissue as the surgical wounds healed.

The researchers also conducted several biocompatibility studies and found that the gel did not cause any side effects.

“A key feature of this new technology is our goal to make it translational. GastroShield was designed to be stored in liquid form in a ready-to-use kit. In addition, it does not require any activation solution, light or activation to form the gel, with the aim to make endoscopic use easy and fast,” says Muñoz, who currently leads the translational effort for GastroShield.

BioDevek is now working to further develop the material for potential use in patients. In addition to its potential use in colonoscopies, this gel could also be useful for treating stomach ulcers and inflammatory conditions such as Crohn’s disease, or for delivering anti-cancer drugs, Artzi says.

The research was funded, in part, by the National Science Foundation.