More than 20 million Americans undergo colonoscopies each year, and in many cases, doctors end up removing polyps that are 2 centimeters or larger and require additional care. This surgery greatly reduces the overall incidence of colon cancer, but it is not without complications, as patients may experience gastrointestinal bleeding during and after surgery.
To prevent these complications from occurring, MIT researchers have developed a new gel, GastroShield, that can be sprayed onto the surgical site through an endoscope. This gel forms a tough yet flexible protective layer that acts as a barrier to damaged areas. The material prevents delayed bleeding and enhances the mechanical integrity of the tissue.
“Our tissue-responsive adhesive technology is engineered to interact with tissue through complementary covalent and ionic interactions as well as physical interactions to provide days of long-term lesion protection against post-polypectomy complications and other wounds that are at risk for gastrointestinal bleeding,” said Natalie Artzi, principal research scientist at MIT’s Institute for Medical Engineering and Science and associate professor of medicine at Harvard Medical School and senior author of the paper.
In an animal study, researchers showed that the GastroShield app integrates seamlessly with current endoscopic surgeries and provides wound protection for three to seven days, helping tissue heal after surgery. Artzi and other members of the research team founded a company called BioDevek, which now plans to further develop the material for use in humans.
BioDevek CEO Gonzalo Muñoz Taboada and BioDevek Chief Scientist Daniel Dahis are the lead authors of the study, which is published in the journal advanced materials. Elazer Edelman, the Edward J. Poitras Professor of Medical Engineering and Science at MIT and director of IMES, and Pere Dosta, a former postdoc in Artzi’s lab, are also authors on the paper.
adhesive gel
Routine colon cancer screening often finds small precancerous polyps that can be removed before they become cancerous. This is usually done using an endoscope. If bleeding occurs during polyp removal, doctors can cauterize the wound to seal it, but this method leaves scars, may delay healing, and lead to other complications.
Additionally, for some patients, bleeding does not occur until several days after surgery. This can be dangerous and may require the patient to return to the hospital for additional treatment. Other patients may develop small tears that allow intestinal contents to leak into the abdomen, leading to serious infection and requiring emergency care.
When tissue needs to be reinforced, doctors often insert metal clips to hold the tissue together, but these cannot be used on larger polyps and are not always effective. Efforts to develop a gel that can seal surgical wounds have not been successful, mainly because the material cannot adhere to the surgical site for more than 24 hours.
The MIT team tested dozens of material combinations that they believed had properties suitable for this use. They wanted to find a formula with a low enough viscosity that it could be easily delivered and sprayed through a nozzle mounted on the end of a catheter inside a commercial endoscope. At the same time, upon tissue contact, the formulation should immediately form a tough gel that adheres firmly to the tissue. They also wanted the gel to be flexible enough to withstand the forces generated by the peristaltic motion of the digestive tract and the food flowing through it.
The researchers came up with a winning combination that included a polymer called Pluronic, a block copolymer that self-assembles into spheres called micelles. These polymers contain multiple amine groups at their ends, which end up on the surface of the micelles. The second component of the gel is oxidized dextran, a polysaccharide that forms strong but reversible bonds with the amine groups of the Pluronic micelles.
Once sprayed, the materials immediately react with each other and the lining of the gastrointestinal tract, forming a solid gel in less than five seconds. The micelles that make up the gel have “self-healing” capabilities, absorbing peristaltic motion and the forces encountered as food moves along the digestive tract by temporarily breaking down and then reassembling.
“To obtain materials that met design criteria and could be delivered through existing colonoscopes, we screened a library of materials to understand how different parameters affect gelling, adhesion, retention and compatibility,” Artzi said.
The protective layer
The gel can also withstand the low pH and enzyme activity in the digestive tract and protect the tissue from the harsh environment while healing itself, highlighting its use in other high-bleeding-risk gastrointestinal wounds, such as gastric ulcers. application potential. More than 4 million Americans do so each year.
In animal tests, the researchers found that every animal treated with the new gel showed rapid sealing and no punctures, leaks or bleeding within a week of treatment. The material lasts about five days, after which it sheds along with the superficial tissue as the surgical wound heals.
The researchers also conducted multiple biocompatibility studies and found that the gel did not cause any adverse effects.
“A key feature of this new technology is that we aim to make it transformable. GastroShield is designed to be stored in a liquid form in a ready-to-use kit. Additionally, it does not require any activation, light or triggering solution to form a gel and is designed to making endoscope use easy and fast,” said Muñoz, who currently leads GastroShield’s transformation efforts.
BioDevek is currently working to further develop the material for patient use. In addition to its potential use in colonoscopies, the gel could be used to treat inflammatory diseases such as gastric ulcers and Crohn’s disease, or to deliver cancer drugs, Artzi said.
The research was funded in part by the National Science Foundation.