A sequential multimodal framework for spinal cord regeneration

This hypothetical study explores a potential therapeutic strategy for patients with recent complete spinal cord injuries (≤6 weeks since injury approximately). We review current literature and identify five key determinants of regenerative failure: inflammation, glial scar formation, deficit in molecular guidance, loss of structural guidance, and persistence of Wallerian debris. Although each of these barriers can be addressed by existing interventions, their efficacy depends partially on a constrained sequence of application. Based on this, a temporally orchestrated strategy is proposed, comprising early immunomodulation to stabilize the lesion environment, mechanical realignment combined with implantation of a temporary extracellular matrix to restore structural continuity, sustained molecular guidance and matrix remodeling to guide axonal growth. The proposed framework offers a mechanistically integrated and testable hypothesis for promoting functional spinal cord regeneration.