Ultra-stable, mucus-inspired hydrogel for strong acid resistance and adhesion in gastric wound healing
Hydrogels are materials like gelatin, which can absorb and retain water, and are used to aid wound healing and enable slow-release drug delivery. However, they usually break down in acidic environments like the stomach. Drawing inspiration from natural properties of gastric mucus, researchers of The Hong Kong Polytechnic University have developed an acid-resistant hydrogel called ultrastable mucus-inspired hydrogel (UMIH), creating a promising platform for biomedical applications.
Prof. WANG Zuankai, Associate Vice President (Research and Innovation), Dean of Graduate School, Kuok Group Professor in Nature-Inspired Engineering and Chair Professor of Nature-Inspired Engineering at PolyU, along with a team of researchers and clinicians from the Sichuan University, has revealed this groundbreaking discovery. The research showed that UMIH significantly improved gastrointestinal wound healing in animals and outperformed a clinically approved mucosal protectant, a material used to protect the stomach lining. The study, titled “Mucus-inspired hydrogels with protonation-driven adhesion for extreme acidic conditions,” has been published in Cell Reports Physical Science.
Prof. WANG said, “Our 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.” Notably, UMIH exhibits remarkable wet adhesion strength (64.7 kPa at pH 2), surpassing that of aluminum phosphate gels by 15-fold, and maintains structural integrity for over 7 days.
UMIH shows promise in treating gastroesophageal reflux, gastric ulcers, and post-surgical wound protection, and can be combined with endoscopic delivery for minimally invasive therapy. In both rat and pig models, it demonstrated strong adhesion and significantly enhanced wound healing.
Like other hydrogels, UMIH consists of a meshwork of polymers that absorb water to create a strong but jelly-like consistency. To enhance its acid resistance, the research team integrated three key molecular components into UMIH’s structure: ELR-IK24, a protein that binds hydrogen ions under acidic conditions to reduce local acidity; tannic acid, which boosts adhesion of hydrogel; and HDI, a molecule that stabilises the hydrogel’s structure under acidic conditions.
“Our hydrogel is a synergistic combination of three molecular components that are all indispensable. This multi-crosslinking architecture keeps UMIH firmly intact in strong acid while maintaining softness and injectability for clinical use,” said Ms Yeung Yeung CHAU, Research Associate of the PolyU Department of Mechanical Engineering and co-author of the research.
In laboratory 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. While 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 its antimicrobial potential.
“UMIH achieves an adhesion strength 15 times higher than that of clinically approved materials under acidic conditions. It remains stable for 7 days and shows excellent biocompatibility and significant tissue repair capability,” said Dr Xiao YANG, Postdoctoral Fellow of the PolyU Department of Mechanical Engineering and co-author of the study.
In pig and rat models of esophageal injury, UMIH adhered firmly 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.
While clinical trials will be needed to validate UMIH’s safety and efficacy in humans, it holds good potential for commercialisation. It is low-cost, easy to mass-produce, and built from components with established safety profiles. The material is ready to use in both operating room and production line. Looking ahead, the research team plans to integrate UMIH with drug release systems and implantable flexible electronics to create smart gastrointestinal devices capable of real-time treatment and monitoring.
Prof. WANG Zuankai, Associate Vice President (Research and Innovation), Dean of Graduate School, Kuok Group Professor in Nature-Inspired Engineering and Chair Professor of Nature-Inspired Engineering at PolyU, along with a team of researchers and clinicians from the Sichuan University, has revealed this groundbreaking discovery. The research showed that UMIH significantly improved gastrointestinal wound healing in animals and outperformed a clinically approved mucosal protectant, a material used to protect the stomach lining. The study, titled “Mucus-inspired hydrogels with protonation-driven adhesion for extreme acidic conditions,” has been published in Cell Reports Physical Science.
Prof. WANG said, “Our 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.” Notably, UMIH exhibits remarkable wet adhesion strength (64.7 kPa at pH 2), surpassing that of aluminum phosphate gels by 15-fold, and maintains structural integrity for over 7 days.
UMIH shows promise in treating gastroesophageal reflux, gastric ulcers, and post-surgical wound protection, and can be combined with endoscopic delivery for minimally invasive therapy. In both rat and pig models, it demonstrated strong adhesion and significantly enhanced wound healing.
Like other hydrogels, UMIH consists of a meshwork of polymers that absorb water to create a strong but jelly-like consistency. To enhance its acid resistance, the research team integrated three key molecular components into UMIH’s structure: ELR-IK24, a protein that binds hydrogen ions under acidic conditions to reduce local acidity; tannic acid, which boosts adhesion of hydrogel; and HDI, a molecule that stabilises the hydrogel’s structure under acidic conditions.
“Our hydrogel is a synergistic combination of three molecular components that are all indispensable. This multi-crosslinking architecture keeps UMIH firmly intact in strong acid while maintaining softness and injectability for clinical use,” said Ms Yeung Yeung CHAU, Research Associate of the PolyU Department of Mechanical Engineering and co-author of the research.
In laboratory 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. While 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 its antimicrobial potential.
“UMIH achieves an adhesion strength 15 times higher than that of clinically approved materials under acidic conditions. It remains stable for 7 days and shows excellent biocompatibility and significant tissue repair capability,” said Dr Xiao YANG, Postdoctoral Fellow of the PolyU Department of Mechanical Engineering and co-author of the study.
In pig and rat models of esophageal injury, UMIH adhered firmly 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.
While clinical trials will be needed to validate UMIH’s safety and efficacy in humans, it holds good potential for commercialisation. It is low-cost, easy to mass-produce, and built from components with established safety profiles. The material is ready to use in both operating room and production line. Looking ahead, the research team plans to integrate UMIH with drug release systems and implantable flexible electronics to create smart gastrointestinal devices capable of real-time treatment and monitoring.
