NSCs Migration Promoted and Drug Delivered Exosomes‐Collagen Scaffold via a Bio‐Specific Peptide for One‐Step Spinal Cord Injury Repair

Abstract Spinal cord injury (SCI) is plaguing medical professionals globally due to the complexity of injury progression. Based on tissue engineering technology, there recently emerges a promising way by integrating drugs with suitable scaffold biomaterials to mediate endogenous neural stem cells (NSCs) to achieve one‐step SCI repair. Herein, exosomes extracted from human umbilical cord‐derived mesenchymal stem cells (MExos) are found to promote the migration of NSCs in vitro / in vivo. Utilizing MExos as drug delivery vehicles, a NSCs migration promoted and paclitaxel (PTX) delivered MExos‐collagen scaffold is designed via a novel dual bio‐specificity peptide (BSP) to effectively retain MExos within scaffolds. By virtue of the synergy that MExos recruit endogenous NSCs to the injured site, and PTX induce NSCs to give rise to neurons, this multifunctional scaffold has shown superior performance for motor functional recovery after complete SCI in rats by enhancing neural regeneration and reducing scar deposition. Besides, the dual bio‐specific peptide demonstrates the capacity of tethering other cells‐derived exosomes on collagen scaffold, such as erythrocytes‐derived or NSCs‐derived exosomes on collagen fibers or membranes. The resulting exosomes‐collagen scaffold may serve as a potential multifunctional therapy modality for various disease treatments including SCI.