Stepwise AIE‐Luminogen Hydrogels for Real‐Time Translation of Wound pH Into Therapeutic Decisions

ABSTRACT The translation of wound microenvironmental chemistry into actionable therapeutic decisions remains a critical challenge in the management of infectious wounds, necessitating real‐time, accurate readouts of infection status and healing progression to avoid over/under‐treatment. Herein, we report step‐wise pH‐responsive hydrogel films that dynamically convert local acid fluctuations into on‐off optical signals, thereby recognizing the phase transition of inflammation to proliferation. Three aggregation‐induced‐emission (AIE) luminogens, TPE‐SA (pK a 5.8), TPE‐SAC (pK a 6.0), and TPE‐SDOX (pK a 6.8), were synthesized and integrated into a high‐tissue‐adhesion hydrogel matrix, which trigger bright fluorescent signal extinguishing via rapid deprotonation transition at respective pK a threshold. Guided by those optical cues, bacterial species, bacterial burden, and infection status associated with pH change were clarified along with the healing process of polymicrobial wounds. The results indicate that the disappearance of TPE‐SDOX hydrogel fluorescence (at pH 6.8) can serve as a precise optical marker for the inflammatory resolution. Compared with the antibiotic overtreatment or undertreatment group, precise treatment reduces drug exposure by 41.3%, while accelerates re‐epithelialization and synchronizes neutrophil apoptosis with angiogenesis. The AIE‐Hydrogel thus closes the “sense–decide–treat” loop, offering a general platform for infection‐precision therapy.