Hydrogels—materials like gelatin that can absorb and hold water—can aid wound healing and enable slow-release drug delivery, but they usually break down in acidic environments like the stomach. Inspired by the properties of gastric mucus, a team of researchers and clinicians led by Zuankai Wang of Hong Kong Polytechnic University have developed an acid-resistant hydrogel called "ultrastable mucus-inspired hydrogel" (UMIH). Publishing September 4 in the Cell Press journal Cell Reports Physical Science, they showed that UMIH improved gastrointestinal wound healing in animals and outperformed a clinically approved mucosal protectant (a material used to protect the stomach lining).
"UMIH has potential for treating gastroesophageal reflux, gastric ulcers, and post-surgical wound protection and can be combined with endoscopic delivery for minimally invasive therapy," says coauthor Bei Li of Sichuan University. "In both rat and pig models, it not only sticks firmly but also helps wounds heal faster and better."
Like other hydrogels, UMIH consists of a meshwork of polymers that absorb water to create a strong but jelly-like consistency. To make it acid resistant, the researchers incorporated three key molecular components into UMIH's structure: a protein called ELR-IK24 that binds to hydrogen ions under acidic conditions to reduce local acidity; tannic acid, which enhances the hydrogel's ability to stick to surfaces; and a molecule called HDI that stabilizes the hydrogel's structure under acidic conditions.
"UMIH represents a major step forward in biomaterials for gastrointestinal repair," says Dr. Wang. "Its strong adhesion, durability, and scalable manufacturing process position it as a promising platform for clinical translation."
In lab tests under acidic conditions (pH2), UMIH showed 15× stronger adhesive abilities compared to aluminum phosphate gel (APG), a clinically approved mucosal protectant and antacid that is used to manage gastric ulcers and acid reflux. And whereas APG degraded completely after 3 days, UMIH still maintained 50% of its structural integrity after 7 days in acidic conditions. UMIH was not associated with any toxicity issues in lab-grown gastrointestinal cells. It also inhibited the growth of E. coli and S. aureus bacteria, indicating that it has antimicrobial potential.
"UMIH achieves an adhesion strength 15 times higher than that of clinically approved materials in acidic conditions," says coauthor Xiao Yang of the Hong Kong Polytechnic University. "It remains stable for 7 days and shows excellent biocompatibility and significant tissue repair capability."
In pig and rat models of esophageal injury, UMIH adhered tightly to wounds and improved healing compared to control animals and animals treated with APG. UMIH was associated with less tissue damage, reduced inflammation, and it promoted the growth of new blood vessels, which is essential for healing.
Clinical trials will be needed to validate UMIH's safety and efficacy in humans, but the researchers say that it has good potential for commercialization.
"This is a material that's ready for both the operating room and the production line," says coauthor Feng Lou of Sichuan University. "UMIH is low-cost, easy –to –mass produce, and built from components with established safety profiles. In [the] future, we plan to integrate UMIH with drug release systems and implantable flexible electronics to create smart gastrointestinal devices that can treat and monitor in real-time."
