3D-printed scaffolds encapsulating red-blood-cell-derived extracellular vesicles for microRNA delivery

This study developed a localized RNA delivery platform that combined red-blood-cell-derived extracellular vesicles with DLP 3D-printed GelMA/PEGDA scaffolds for spinal cord injury repair. RBCEVs showed strong cytocompatibility in primary CNS cells and cell-type-specific uptake, with the highest internalization and gene-silencing efficiency in oligodendrocyte precursor cells, where uptake exceeded 70% and gene silencing reached 74.2%. Embedding RBCEVs into printed microchannel scaffolds enabled sustained release of miR-219 and miR-338 for more than 21 days while preserving vesicle structure and bioactivity. In vitro, this system promoted OPC differentiation, increased MBP-positive mature oligodendrocytes, and enhanced myelination. In a rat complete transection spinal cord injury model, scaffold-mediated delivery increased CC1-positive mature oligodendrocytes, reduced PDGFRα-positive OPCs, and shifted microglia toward a more anti-inflammatory phenotype, supporting scaffold-based RBCEV delivery as a promising regenerative strategy for CNS remyelination.