Biomimetic nanomaterial-based strategies for spinal cord injury repair

Spinal cord injury (SCI) poses significant clinical challenges marked by profound functional impairments and limited clinical interventions due to its complex pathological microenvironment and limited intrinsic regenerative capacity. This review systematically explores the pathophysiology of SCI, emphasizing key therapeutic targets in neuroprotection, axon regeneration, and immunomodulation. We innovatively propose a functional classification framework to categorize synthetic nanomaterials into (1) targeted drug delivery systems, (2) nanoparticle-hydrogel hybrid systems and (3) stimuli-responsive functional nanoparticles, effectively resolving overlaps in traditional classifications. Furthermore, biogenic nanomaterials—including exosomes, cell membrane-coated systems, and decellularized extracellular matrix (ECM) scaffolds—are highlighted for their innate biocompatibility, immune evasion, and bioactivity. These biogenic nanomaterials synergize with advanced technologies such as genetic engineering and combinatorial therapies to enhance neural repair. Particularly, we provide the first systematic comparison of microstructural differences in decellularized scaffolds derived from diverse tissues (e.g., spinal cord, optic nerve, sciatic nerve) and their mechanisms in guiding axonal regeneration. Despite promising preclinical outcomes, challenges such as standardization, scalable production and long-term biosafety remain in the gap between experimental models and clinical applications. Future directions focus on dynamic responsiveness, multifunctional combinatorial designs and integration with regenerative medicine paradigms to achieve functional recovery in SCI management. • Comprehensive pathophysiology overview of SCI, emphasizing ferroptosis and axonal regeneration barriers. • Novel functional classification of synthetic nanomaterials resolves overlap issues. • Biogenic nanomaterials review: exosomes, membrane-coated systems, decellularized scaffolds & therapeutic mechanisms. • Clinical translation analysis identifies key challenges and future design strategies.