Dual-Cues Laden Scaffold Facilitates Neurovascular Regeneration and Motor Functional Recovery After Complete Spinal Cord Injury

Abstract

Complete transection spinal cord injury (SCI) severely disrupts the integrity of both neural circuits and the microvasculature system. Hence, fabricating a functional bio-scaffold that could coordinate axonal regeneration and vascular reconstruction in the lesion area may emerge as a new paradigm for complete SCI repair. In this study, a photosensitive hydrogel scaffold loaded with collagen-binding stromal cell-derived factor-1a and Taxol liposomes is capable of inducing migration of endothelial cells and promoting neurite outgrowth of neurons in vitro. In addition, when implanted into a rat T8 complete transection SCI model, the above dual-cues laden scaffold exhibits a synergistic effect on facilitating axon and vessel regeneration in the lesion area within 10 days after injury. Moreover, long-term therapeutic effects are also observed after dual-cues laden scaffold implantation, including revascularization, descending and propriospinal axonal regeneration, fibrotic scar reduction, electrophysiological recovery, and motor function improvement. In summary, the dual-cues laden scaffold has good clinical application potential for patients with severe SCI.

Keywords: axon regeneration; complete spinal cord injury; hydrogel scaffold; neurovascular regeneration.