Bioadhesive hydrogels demonstrating pH-independent and ultrafast gelation promote gastric ulcer healing in pigs

Abstract

Hydrogels are soft materials used in an array of biomedical applications. However, the in situ formation of hydrogels at target sites, particularly in dynamic in vivo environments, usually requires a prolonged gelation time and results in poor adhesion. These limitations cause considerable loss of both hydrogel mass and encapsulated therapeutic cargoes, thereby compromising treatment outcomes. Here, we report the development of a hydrogel based on thiourea-catechol reaction to enhance the bioadhesion. Compared with classical bioadhesive hydrogels, our hydrogels show enhanced mechanical properties, exceedingly short curing time, and pH-independent gelation with a much lower oxidant concentration. We further report the robust adhesion of our hydrogels to acidic gastric tissues and easy delivery to the porcine stomach via endoscopy. The delivered hydrogels adhered to ulcer sites in vivo for at least 48 hours. Hydrogel treatment of gastric ulcers in rodent and porcine models accelerated ulcer healing by suppressing inflammation and promoting re-epithelization and angiogenesis. The improved retention of proregenerative growth factors and reduced exposure to external catabolic factors after hydrogel application may contribute to the observed therapeutic outcomes. Our findings reveal a promising biomaterial-based approach for treating gastrointestinal diseases.