Application and Future Perspectives of Extracellular Vesicle-Loaded Scaffold in Spinal Cord Injury

Following the initial trauma of spinal cord injury (SCI), the secondary injury phase-characterized by inflammation, oxidative stress, neuronal death, and axonal demyelination-establishes an adverse microenvironment that hinders functional recovery. Despite the availability of existing clinical therapies, they often yield suboptimal functional recovery. In this review, the applications and future prospects of extracellular vesicle (EV)-loaded scaffolds for SCI repair are summarized. This review discusses the biological properties and therapeutic action of EVs, as well as limitations of using them as a single agent, such as rapid clearance and poor targeting. Other scaffold loading strategies and types that change in response to the microenvironment are also reviewed. This review highlights the advancement of EV-loaded scaffolds in alleviating secondary injury, controlling inflammation, enhancing neural regeneration and remyelination, and promoting angiogenesis. Microvesicles, a high-capacity and large subtype of EVs with rapid release and functional surface proteins, in particular, have been shown to have multi-target repair capabilities in various disease models. Their integration with scaffolds for SCI is suggested as a promising translational direction. Current challenges encompass subtype standardization, safety evaluation, as well as large-scale production. The review concludes that EV-loaded scaffolds are not just delivery systems, but a regenerative platform that enables spatiotemporal structure-signal synergy. Subtype-specific selection, pathology-stage-directed release, and industry-compliant quality control should be the focus in future studies to develop this strategy beyond basic research into clinical translation.