Slug-Inspired Hydrogel Successfully Seals Gastrointestinal Fistulas in Animal Trials

The binding constraint for treating gastrointestinal fistulas has always been the wet, highly active environment of the digestive tract, which routinely defeats traditional clips and sutures. Now, researchers have engineered a thermoresponsive hydrogel that mimics the defensive mucus of slugs to solve this exact problem.[1][2]

The material, developed by a team at the Chinese Academy of Sciences and the China-Japan Friendship Hospital, can be injected as a liquid through a standard endoscope. Once it hits the 37-degree Celsius environment of the body, it solidifies into a gel in approximately 30 seconds.[1][2]

The findings, published on October 30 in Nature Biomedical Engineering, demonstrate that the hydrogel successfully sealed 20-millimeter gastric fistulas in Bama miniature pigs. After 14 days, the fistulas had closed completely with smooth mucosal healing and no foreign-body residue.[1][3]

Gastrointestinal fistulas—abnormal passages that leak digestive fluids into the abdomen or other organs—are a severe complication of surgery, trauma, or tumors. The condition carries high mortality rates, and open surgical repair is often too traumatic for already compromised patients.[2]

"Current endoscopic fistula treatments have limitations, though: Stents migrate, fistulas closed with titanium clips recur, and endoscopic suturing is technically challenging," the Chinese Academy of Sciences noted in its institutional release. Postoperative tissue adhesion further complicates these conventional clinical treatments.[2]

To overcome these hurdles, the research team looked to nature. Slugs in humid jungles secrete a defensive mucus rich in positively charged proteins that firmly attaches tree frogs to branches, relying on electrostatic interactions to grip wet tissue.[2]

The engineered sealant, named PGaIII, replicates this mechanism by combining linear poly(N-isopropylacrylamide) with gallium ions. The result is a Janus-type adhesion, meaning the material is highly sticky on the side touching the tissue, but non-sticky on the side facing the digestive tract.[1][2]

This double-sided asymmetry forms in a single step during injection, which the researchers termed slug-inspired electrostatically assisted topological Janus adhesion. It eliminates the need for clinicians to handle a pre-formed patch or mix materials during the procedure.[2]

In laboratory testing, the adhesive side of the hydrogel demonstrated a shear strength of 10.46 kilopascals, nearly 100 times stronger than the non-adhesive side. In an ex vivo porcine stomach model, the gel successfully sealed a 10-millimeter perforation without any leakage.[2]

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The material also actively shrinks by about 51.6 percent after application. This centripetal traction force pulls the surrounding tissue together, avoiding the common hydrogel problem of swelling, which can inadvertently widen the fistula opening and worsen the leak.[2]

Beyond its mechanical properties, the gallium ions in the hydrogel interfere with bacterial iron metabolism. The researchers reported an inhibition efficiency of 98.6 percent against common pathogens like Escherichia coli and Staphylococcus aureus, adding a crucial antibacterial defense to the wound site.[2]

While the animal trials are promising, the material remains in the preclinical stage. The Bama miniature pig model was chosen because its gastrointestinal anatomy closely resembles that of humans, but human clinical trials are still years away.[1][2]

"We will further study the metabolism and clearance of Ga3+ in large animals and the influence of gastrointestinal pH fluctuations on the degradation rate," Professor Bai Shuo, the study's lead author, said in the institutional release. The team must ensure the metal ions do not accumulate toxically over time.[2]

The researchers also plan to optimize the catheter delivery system and the manufacturing process to prepare the hydrogel for eventual clinical translation. If successful, the material could be adapted to repair fistulas in other organs, offering a new standard for minimally invasive surgical sealing.[2][3]