Porous microneedle patch with sustained exosomes delivery repairs severe spinal cord injury

Abstract: The transplantation of mesenchymal stem cells-derived exosomes (MSC-EXO) has been suggested as an efficacious treatment to suppress SCI-triggered neuroinflammation. However, an ethically acceptable method to continuously deliver MSC-EXO into the acute spinal lesion without damaging spared tissues/axons has never been achieved. In this study, we fabricated a device that consists of a patch containing MSC and microneedle array (MN-MSC patch) to treat severe SCI. When topically applied to the acute spinal lesion beneath spinal dura, the soft microneedle (MN) array with good mechanical strength avoids damages to the spared spinal tissues and the porous microstructure of MN facilitates highly efficient MSC-EXO delivery. With the capacity to sustainedly deliver MSC-EXO, the MN-MSC patch was evaluated in a contusive rat SCI model and showed that the MSCs encapsulated in the patch could survive for at least 7 days, which covers the optimal time window for down-regulating SCI-triggered neuroinflammation. As a result, the MN-MSC patch treatment leads to reduced cavity and scar tissue formation, angiogenesis, and the survival of spared tissues/axons. Remarkably, the rats treated by this method achieved superior muscle control and exhibited robust hindlimb locomotion functional recovery. Conclusively, the MN-MSC patch device proposed here breaks through the current dilemma from the contradiction between treatment efficacy and ethical issues in treating acute SCI.