Endoscopically Deliverable Polymer Adhesives with pH-Triggered Multiple Molecular Evolution for Gastric Ulcer Repair

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Gastroenterology

Background:

• Hydrogel adhesives show potential for treating gastric ulcers.
• Existing hydrogels face challenges in endoscopic delivery, wet adhesion, and gastric retention.

Purpose of the Study:

• To engineer a sequential pH-responsive adhesive (PNMH) for enhanced gastric ulcer treatment.
• To investigate the pH-triggered evolution of intermolecular interactions in PNMH.
• To evaluate the adhesive properties, retention, and in vivo efficacy of PNMH for gastric ulcer healing.

Main Methods:

• PNMH was synthesized via polymerization of β-carboxylic-amide-functionalized N-acryloyl phenylalanine and hydroxyethyl acrylamide.
• The pH-triggered evolution of intermolecular interactions was studied.
• Adhesion strength, gelation time, and in vivo residence time were evaluated.
• Efficacy in protecting ulcers and promoting healing was assessed in rat and pig models.

Main Results:

• PNMH exhibits ultrafast gelation (~4 s) in gastric acid.
• Achieves immediate wet tissue adhesion (~24.1 kPa), intensifying to 34.3 kPa.
• Demonstrates long-term integration (>30 days) and prolonged in vivo residence time (>4 days).
• Effectively shields ulcers, attenuates immune response, and promotes mucosal healing.

Conclusions:

• PNMH presents an advanced molecular design for gastric-resistant polymer adhesives.
• The sequential pH-responsive mechanism enables robust adhesion and rapid gelation.
• PNMH is a promising candidate for clinical gastric ulcer treatment.