Microenvironment-responsive therapeutic platforms: Innovations for spinal cord injury repair

• • Microneedle-mediated delivery achieves direct intraparenchymal administration, bypassing the blood-spinal cord barrier and improving local drug bioavailability by an order of magnitude compared to systemic injection, as evidenced by the platform's design for spinal cord injury repair. • • Ferroptosis inhibition via iron chelation and GPX4 stabilization reduces lipid peroxidation byproducts (e.g., malondialdehyde) and mitigates secondary injury, a critical bottleneck in SCI therapy where oxidative stress peaks within 24–72 hours post-injury. • • Hydrogen therapy scavenges hydroxyl radicals and peroxynitrite with high selectivity, offering a non-toxic, anti-inflammatory modality that complements conventional pharmacotherapy; the platform's microenvironment-responsive release ensures sustained hydrogen delivery at the lesion site. • • The integration of microneedle, ferroptosis, and hydrogen modalities represents a combinatorial strategy that addresses multiple pathological pathways simultaneously, potentially reducing glial scar formation and promoting axonal regeneration, as supported by the National Natural Science Foundation of China (82574518).