Biomaterial-Based Controlled Release Systems for Spinal Cord Remyelination

Spinal cord injury (SCI) triggers a complex secondary injury cascade characterized by oligodendrocyte (OL) death and axonal demyelination, leading to permanent neurological deficits. Despite the presence of endogenous oligodendrocyte progenitor cells (OPCs), the inhibitory microenvironment-marked by inflammation, glial scarring, and biochemical barriers-prevents effective remyelination. Traditional pharmacological treatments are further hindered by the blood-spinal cord barrier and rapid clearance of intrathecal injections. This review examines the evolution of controlled release systems engineered to modulate the oligodendroglial lineage. We analyze macro- and micro-scale platforms, including scaffolds, which provide mechanical and topographical cues to direct the fate of OLs and OPCs. Furthermore, we discuss advanced nanoscale vectors, such as nanoparticles and exosomes, designed to deliver high-value payloads-including small molecules and therapeutic oligonucleotides-directly to the lesion site while minimizing systemic toxicity. Finally, we address critical translational gaps to bridge the divide between preclinical innovation and clinical application in restoring neural connectivity.