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The complex biochemical environment, rapid turnover of mucus and surface epithelium, and constant motility in the gastrointestinal (GI) tract present significant challenges for disease treatment, creating an environment that is inhospitable for the retention of biomedical materials and devices. 

Current treatments and tools, such as endoclips, are ineffective for long-term therapeutic delivery due to the ever-changing nature of the GI tract. Mucosal adhesives have been explored as treatments, but existing options only adhere for up to 24 hours.  

To extend the mucosal retention time, adhesives must be able to penetrate the mucosal layer and interact with the deeper epithelium, which has a slower turnover rate, giving hydrogel adhesives the potential to last longer. Until now, scientists have been unable to find a way to create this penetration and adhesion. In a new paper, available now in Science Translational Medicine, MechE researchers introduce e-GLUE, a novel hydrogel interface that uses electroadhesion to both penetrate and adhere to the mucosal lining of the GI tract.  

e-GLUE, a new electroadhesive hydrogel, may be used to deliver sustained drug administration for GI diseases and biosensing. Photo: Courtesy of the researchers

Electroadhesion, which works like a mini electrical charge, helps the hydrogel ‘stick’ to the GI lining. With a brief electrical stimulation, e-GLUE is able to diffuse into the deep mucosal epithelium, increasing adhesion as well as gastric mucosal retention for up to 30 days. This can be effective for treatments in GI bleeding, localized drug delivery, and biosensing. In addition, e-GLUE is beneficial due to its ability to mimic tissue strength while also being stretchable and biocompatible.  

The idea for e-GLUE first came about when Binbin Ying, a Banting Postdoctoral Fellow in the Mechanical Engineering department and research fellow at Brigham and Women's Hospital, Harvard Medical School, was doing his doctoral studies. He, along with other researchers, were able to mimic a diode, meaning a way to convert electricity into energy. They did this by stacking polyanions and polycations, which are oppositely charged polymers, thereby creating a dual-layer ionic hydrogel.  

At MIT, Ying and his colleagues, including Giovanni Traverso, associate professor of mechanical engineering and Karl Van Tassel (1925) Career Development Professor and Robert Langer, David H. Koch (1962) Institute Professor, built on that foundation. They realized that electrical stimulation could manipulate these ions to penetrate the mucosal barrier of the GI tract, increasing adhesion strength and duration. 

e-GLUE, composed of cationic polymers and a hydrogel matrix, facilitates active polymer diffusion into deep mucosal layers. It is delivered by connecting the electrode via two wires to an external power source in the endoscopic channel. After just one minute of electrical stimulation, these polymers interact with proteins in mucosal tissue. The process increases adhesion 30-fold. In vivo retention in porcine stomach models showed that e-GLUE can last for over 30 days, which is significantly longer than the current 24-hour maximum that other hydrogel adhesives employ.  

The researchers tested e-GLUE in several models and observed that despite intraluminal fluids and mucus layers, which typically inhibit the ability of hydrogel to stick to the GI tract, it was able to retain its adhesiveness.  

The next step involved finding the right amount of heat to make the hydrogel effective without burning. After testing various electrical stimulation parameters, it was discovered that 10V for 80 seconds was optimal for adhesion without overheating. X-rays confirmed that gastric retention lasted 11 to 30 days, and colonic retention 4 to 8 days. This means e-GLUE can stay in place up to 15 times longer than current adhesives, which only last two days. 

In addition, testing shows that e-GLUE had no adverse effects. “In our comprehensive studies involving pigs, we observed no behavioral changes during extensive monitoring periods,” said Ying. He added that the utilization of electric stimulation as a vehicle for translational applications improves e-GLUE’s comfort and safety. In addition, histological evaluations up to 60 days showed no scarring or inflammation.  

The potential impact on medicine is significant. Because e-GLUE has demonstrated nearly instant mucosal sealing and sustained localized therapeutic delivery, it may be used to stop GI bleeding by providing rapid hemostasis and tissue sealing, which can be lifesaving. It also may be used to deliver sustained drug administration for GI diseases such as inflammatory bowel disease, while also minimizing side effects. In addition, e-GLUE can be used in biosensing for long-term physiological monitoring and diagnostics.  

Another benefit of e-GLUE is that the body will naturally break it down. “The beauty of electroadhesion is its reversibility; applying reverse electrical stimulation allows the hydrogel to be easily peeled off,” says Ying. 

Collaborating researchers from the MIT Mechanical Engineering department include Kewang Nan, Hana Ro, Karen Jiang, Josh Jenkins, Andrew Pettinari, Johannes Kuosmanen, Niora Fabian, Aaron Lopes, and Alison Hayward. Researchers from the Brigham and Women’s Hospital, Zhejiang Pharmaceutical University, the David H. Koch Institute for Integrative Cancer Research, and McGill University also contributed to the project. 

The full research paper, “An electroadhesive hydrogel interface prolongs porcine gastrointestinal mucosal theranostics,” appears in the journal Science Translational Medicine.