Precision Nanomedicine for Traumatic Neural Injury: Functional Paradigms and Translational Frameworks

Traumatic neural injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), and peripheral nerve injury (PNI), impose a substantial global burden. These injuries converge on oxidative stress, neuroinflammation, regulated cell death, demyelination, and extracellular matrix remodeling, while diverging in timing, cellular effectors, and regenerative capacity. Current management still fails to arrest secondary injury or restore functional neural circuitry. Nanomedicine integrates targeted delivery, microenvironmental regulation, and regenerative support, yet existing strategies and reviews remain compartmentalized by injury type or material class. Such fragmentation constrains the integration of shared mechanisms with injury-specific requirements. To address this gap, we develop a cross-injury framework for nanoparticle-based intervention. Separate reanalysis of three single-cell datasets suggests recurrent myeloid involvement and injury-specific within-dataset patterns. We compare lipid-based, polymeric, inorganic, carbon-based, biomimetic, and hybrid platforms in relation to physicochemical properties and biological fate. Six paradigms are organized by pathological need: scaffold construction and microenvironment remodeling, topographical guidance, biomimetic targeting, endogenous stimulus-responsive release, external physical-field activation, and intracellular reprogramming. We trace evolution from passive encapsulation to multi-omics-guided and artificial intelligence (AI)-assisted precision design and examine barriers to manufacturing, biodistribution, safety, protein-corona control, and regulatory evaluation. This framework connects injury mechanisms, functional needs, and material selection to guide translation.