Mucus-inspired hydrogels with protonation-driven adhesion for extreme acidic conditions

Despite their biomedical promise due to biocompatibility and flexibility, conventional hydrogels exhibit limited adhesion and structural stability under highly acidic conditions (pH ≈ 2) due to acid-induced network degradation. Inspired by the protective properties of gastric mucus, we developed an ultrastable mucus-inspired hydrogel (UMIH) for extreme acidic environments. The UMIH achieves remarkable wet adhesion strength (64.7 kPa at pH 2), surpassing aluminum phosphate gels by 15-fold, and maintains structural integrity for over 7 days. Its design incorporates high-isoelectric-point (HIP) proteins for protonation-driven electrostatic interactions, tannic acid for hydrogen bonding and hydrophobic interactions, and hexamethylene diisocyanate as a covalent crosslinker. Additional physical crosslinking between HIP and tannic acid further enhances robustness. In vivo porcine esophageal injury models confirmed the UMIH's exceptional performance in adhesion, epithelial remodeling, and accelerated tissue repair. These findings establish the UMIH as a transformative platform for biomedical applications requiring durable adhesion and structural ability in challenging physiological environments.