Self-adaptive hydrogels for treatment of spinal cord injury

Spinal cord injury (SCI), characterized by a sequential, spatiotemporally heterogeneous pathological progression encompassing primary injury, acute/subacute, intermediate and chronic phases, remains a devastating clinical challenge with limited effective therapies. Conventional hydrogel-based delivery system cannot dynamically match the spatiotemporally evolving pathological microenvironment of SCI, whereas self-adaptive hydrogels can recognize the dynamic pathological cues within the lesion microenvironment, and undergo programmable adjustments to their structural and functional properties, establishing a bidirectional adaptive interaction with the pathological microenvironment to achieve on-demand release and therapeutic regulation. In this review, we propose a pathology-driven analytical framework for the self-adaptive hydrogels in SCI repair, focusing on the intrinsic linkage between stage-specific SCI pathological characteristics, rational material design, and corresponding therapeutic outcomes. We first outline the full temporal pathological landscape of SCI and clarify the distinct therapeutic requirements of each injury phase, and then systematically classify and evaluate the self-adaptive hydrogel delivery systems in accordance with their suitability for different pathological stages, establishing a rigorous logical chain from pathological cue recognition, targeted adaptive material design to mechanism-based therapeutic validation. We further summarize the core design principles and multifunctional therapeutic roles of such adaptive systems, and finally discuss the key challenges in clinical translation and future development directions. • Pathology-driven framework guides design of self-adaptive hydrogels for SCI repair. • Conventional hydrogels mismatch the dynamic pathological microenvironment of SCI. • Self-adaptive hydrogels enable targeted modulation of acute SCI microenvironment. • Self-adaptive hydrogels support on-demand release for chronic neural regeneration. • Critical analysis evaluates clinical potential of self-adaptive hydrogels in SCI.