Each year, over 15 million colonoscopies are carried out in the United States, and in 20% of those procedures, gastroenterologists remove precancerous growths from the colon.
These early-stage lesions are known as polyps, and removing these growths is the best approach to prevent the development of colon cancer.
Physicians usually administer a saline solution within the space beneath the lesion to make sure that the colon is not damaged during the procedure. This process creates a “cushion” that lifts the polyp and thus makes it easier to remove it safely. This cushion, however, does not last for a long time.
Now, MIT researchers have come up with an alternative method—a solution that can be injected as a liquid but changes into a solid gel as soon as it reaches the tissue, forming a cushion that is more stable and lasts for a longer time.
That really makes a huge difference to the gastroenterologist who is performing the procedure, to ensure that there’s a stable area that they can then resect using endoscopic tools.
Giovanni Traverso, Assistant Professor, Department of Mechanical Engineering, MIT
Traverso is also a gastroenterologist at Brigham and Women’s Hospital, and is the senior author of the study, which has been published in the July 30th, 2019 issue of Advanced Science. Former MIT postdocs Jinyao Liu and Yan Pang are the lead authors of the study.
Other authors include technical associate Joy Collins, MIT undergraduate Zaina Moussa, Division of Comparative Medicine veterinarian Alison Hayward, former technician Shane McDonnell, David H. Koch Institute Professor Robert Langer, and Brigham and Women’s Hospital gastroenterologist Kunal Jajoo.
A Stable Cushion
Although several colon polyps are not harmful, some can ultimately turn out to be cancerous if not eliminated. This procedure is usually performed by gastroenterologists during a routine colonoscopy. Here, a lasso-like tool is used to capture the tissue before it is cut off.
During this procedure, there are certain risks of tearing the colon lining, prompting doctors to often inject saline into the space just beneath the lining—known as the submucosal space—in order to lift the polyp away from the colon’s surface.
“What that does is separate those tissue layers briefly, and it gives one a little bit of a raised area so it’s easier to snare the lesion,” Traverso stated. “The challenge is that saline dissipates very quickly, so we don’t always have enough time to go in and intervene, and may need to reinject saline.”
It can take 10 to 20 minutes, or even longer, to remove complex lesions; however, the saline cushion will last only for a few minutes. While scientists have attempted to extend the life of the cushions by adding thickening agents like cellulose and gelatin, it is very difficult to inject these substances via the narrow needle utilized for the procedure.
In order to resolve that problem, the MIT researchers decided to develop a shear-thinning gel. Under normal conditions, this material exists in semisolid gels but when a force is exerted on it, its viscosity reduces which allows it to flow more easily. This implies that the material can be easily administered via a narrow needle and subsequently converted back into a solid gel as soon as it enters into the colon tissue.
Many different kinds of materials can be used for making shear-thinning gels. For this purpose, the team decided to use a combination of two biocompatible materials that can create gels— alginate, a polysaccharide extracted from algae, and Laponite, a powdery clay employed in cosmetics and many different products.
We chose these materials because they are biocompatible and they allow us to tune the flowing behavior of the resulting gels.
Yan Pang, Former Postdoc, MIT
With the help of these materials, the scientists produced a shear-thinning gel that can be injected in pigs to create a stable cushion for over an hour. This would provide gastroenterologists plenty of time to eliminate the polyps.
“Otherwise, you inject the saline, then you change tools, and by the time you’re ready the tissue is kind of flat again. It becomes really difficult to resect things safely,” stated Traverso.
According to Jay Pasricha, a professor of medicine and neuroscience at Johns Hopkins School of Medicine, this method could provide “an elegant solution” to the issue of keeping lesions elevated at the time of surgical removal.
It’s a growing unmet need. In the last decade, we’ve shifted toward trying to resect more complex tumors from the colon endoscopically, rather than through traditional forms of surgery. It would be great to have a material that can last throughout the duration of the procedure.
Jay Pasricha, Professor, Medicine and Neuroscience, Johns Hopkins School of Medicine
Pasricha was not involved in the study.
By changing the composition of the gel components, the scientists can regulate features like viscosity, which has an impact on the duration the cushion remaining stable. If this kind of injectable gel is made to last longer, it can prove handy for applications like narrowing the GI tract, which can possibly be used for preventing acid reflux or helping with weight loss in people by making them feel full.
In addition, the injectable gel could be used for delivering drugs to the intestinal tract, according to Traverso.
Moreover, the scientists discovered that the material does not cause any adverse side effects in pigs. As such, the team is hoping to initiate trials in human patients in the next three to five years.
“This is something we think can get into patients fairly quickly,” Traverso added. “We’re really excited about moving it forward.”
The National Institutes of Health, the Alexander von Humboldt Foundation, the Division of Gastroenterology at Brigham and Women’s Hospital, and the MIT Department of Mechanical Engineering funded the study.