Self-Healing and pH-Robust Hydrogels Enabled by Synergistic Supramolecular Interactions for Injectable Gastrointestinal Wound Repair.

Injectable self-healing hydrogels are promising biomaterials for minimally invasive internal wound repair. However, most hydrogels fail in the gastrointestinal tract, where extreme pH fluctuations, from strong acidity to mild alkalinity, disrupt conventional cross-linking interactions and lead to network dissociation. In this work, we report an injectable self-healing and pH-robust hydrogel dressing that withstands diverse gastrointestinal conditions by leveraging cooperative supramolecular interactions. Specifically, the integration of π-cation-π and hydrophobic interactions imparts the hydrogel with exceptional thermo-responsiveness, high injectability, rapid in situ gelation property, and robust self-healing capability, independent of environmental fluctuations. Furthermore, the hydrogel effectively resists bacterial adhesion and prevents biofouling, owing to the strong hydration shell formed by the hydrophilic chains within the network. In vivo studies using rat models demonstrate that the hydrogel readily adapts to both gastric and intestinal wound sites, simplifying the surgical procedure compared with sutures and commercial barrier films, which significantly reduces postoperative complications such as adhesion and inflammation while accelerating the healing of gastrointestinal perforations. This work establishes a supramolecular design strategy for engineering multifunctional, environment-adaptive biomaterials, opening new avenues for internal wound repair and other challenging biomedical applications.