A Functional Supramolecular Hydrogel with Host−Guest Cyclodextrin Co-Delivery of Curcumin and Borneol Actively Remodels the Pathological Microenvironment of Oral Ulcers

Abstract Oral ulcer healing is hindered by a pathological microenvironment characterized by reactive oxygen species (ROS) accumulation, bacterial biofilms, and persistent inflammation. Here, we develop a supramolecular hydrogel integrating cyclodextrin-based co-inclusion with an injectable thermoresponsive ABA triblock copolymer for microenvironmental regulation. Cyclodextrin enables efficient co-loading of curcumin and borneol, enhancing their solubility and stability. The resulting inclusion complexes are incorporated into a poly(N-isopropylacrylamide)-based copolymer bearing adhesive phenylboronic acid moieties, yielding an injectable hydrogel with thermoresponsive gelation, tissue adhesion, and dynamic crosslinking. The hydrogel achieves >80% free radical scavenging and broad-spectrum antibacterial activity in vitro. In a rodent oral ulcer model, it promotes healing by scavenging ROS, suppressing bacterial growth, promoting M2 macrophage polarization, and enhancing angiogenesis. This multifunctional hydrogel provides an active microenvironment-regulating strategy for oral ulcer treatment.