Treating wounds and delivering drugs in the gastrointestinal tract is challenging because most biomaterials rapidly degrade in the stomach’s highly acidic environment. Conventional hydrogels lose adhesion and structural integrity, limiting their effectiveness for gastric ulcers and post-surgical repair. Researchers have now developed an ultra-stable hydrogel that remains intact and strongly adhesive even under extreme acidity, enabling durable wound protection and targeted drug delivery in the stomach.

The ultra-stable mucus-inspired hydrogel, or UMIH, developed by researchers at The Hong Kong Polytechnic University (PolyU, Hong Kong, China), in collaboration with Sichuan University (Chengdu, China), is designed to replicate the protective properties of natural gastric mucus. The material combines a proton-binding protein, tannic acid to enhance adhesion, and a stabilizing crosslinker to maintain integrity in acidic conditions.

Researchers evaluated UMIH under simulated gastric conditions and compared its performance with aluminum phosphate gel, a clinically approved mucosal protectant. Adhesion strength, structural stability, and degradation were assessed at low pH, alongside in vitro biocompatibility testing on gastrointestinal cells. The hydrogel was also tested in rat and pig models of esophageal injury to assess wound coverage, inflammation, and tissue repair.

Under pH 2 conditions, UMIH achieved a wet adhesion strength of 64.7 kilopascals, around 15 times higher than that of aluminum phosphate gel. While the conventional gel fully degraded within three days, UMIH retained about 50% of its structure after seven days. Animal studies showed improved wound healing, reduced inflammation, and enhanced blood vessel formation, with no detectable toxicity and additional antibacterial activity against common pathogens. The findings were published in Cell Reports Physical Science.

UMIH could be used to treat gastric ulcers, gastroesophageal reflux, and post-surgical gastrointestinal wounds, as well as to support minimally invasive endoscopic drug delivery. Its low cost, scalability, and stability make it suitable for large-scale manufacturing and clinical translation. Future work will explore integrating the hydrogel with controlled drug release systems and implantable flexible electronics for smart gastrointestinal therapies.

“UMIH shows promise in treating gastroesophageal reflux and gastric ulcers, and in protecting post-surgical wounds,” said Zuankai Wang, PhD, lead investigator of the study. “It can also be combined with endoscopic drug delivery for minimally invasive therapy. This research establishes UMIH as a transformative, extremely acid-tolerant platform, with immediate applications in gastrointestinal repair and targeted drug delivery, while also opening avenues for next-generation implantable devices to accelerate translation to the clinic.”

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