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Pathologically, secondary injuries trigger a series of physical and chemical signals, including dysregulated pH, elevated ROS, increased enzyme activity, excessive inflammation, and altered biophysical cues. To date, implanting microenvironment\u2010responsive biomaterials at the SCI lesion site has been shown to ameliorate the pathological microenvironment by recognizing and neutralizing these signals. Moreover, by exploiting disease\u2010specific signals as triggers for controlled\u00a0drug release, microenvironment\u2010responsive biomaterials improve the accuracy and effectiveness of treatments. This review focuses on design principles, response mechanisms, characteristics, and diverse types of SCI microenvironment\u2010responsive biomaterials. 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