In response to the comprehensive review by Zhang et al. on nanomaterials for spinal cord injury (SCI) repair, this commentary provides a critical perspective on the formidable translational challenges that must be addressed. While the potential of nano-scaffolds and targeted delivery systems is evident, we argue that the field is hampered by an overreliance on acute rodent models which poorly recapitulate complex chronic human SCI pathology. Significant concerns regarding long-term biocompatibility, degradation kinetics, and potential immunogenicity remain inadequately explored. Furthermore, the complexity of combinatorial strategies introduces substantial manufacturing and regulatory hurdles. We contend that future progress requires a paradigm shift towards a more integrated development philosophy. This entails adopting a staged, complementary preclinical model strategy, designing next-generation “smart” systems with regulatory feasibility as a core principle from inception, and incorporating rigorous safety and manufacturing sciences. Only through such a balanced, interdisciplinary approach can nanomaterial-based therapies hope to achieve meaningful clinical translation for SCI.
Yang et al. (Thu,) studied this question.