Advances in Microenvironment-Responsive Biomaterials for Spinal Cord Injury Repair

Spinal cord injury (SCI) often leads to permanent motor and sensory functional loss, accompanied by a dysfunctional pathological microenvironment. 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-responsive biomaterials at the SCI lesion site has been shown to ameliorate the pathological microenvironment by recognizing and neutralizing these signals. Moreover, by exploiting disease-specific signals as triggers for controlled drug release, microenvironment-responsive biomaterials improve the accuracy and effectiveness of treatments. This review focuses on design principles, response mechanisms, characteristics, and diverse types of SCI microenvironment-responsive biomaterials. In addition, the recent advances, regeneration mechanism, preclinical applications, clinical translation prospects, current challenges, and future developments are summarized, aiming to provide theoretical guidance for the development of advanced biomaterial-based therapeutic strategies.