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.

Advances in Biomaterial‐Based Spinal Cord Injury Repair

“…[ 76 ] We have developed a visible‐light crosslinked gelatin hydrogel for the localized delivery and sustained release of biological cues, which could gelatinize the damaged area and precisely fit the lesion shape. [ 76a,77 ]…”

“…[ 126 ] Compared to natural proteins, recombinant CBD‐proteins exhibited superior sustained release behavior, prolonged retention at high concentrations, and robust bioactivity on the collagen scaffold within the injured spinal cord. [ 70b,77,126c,127 ] The aligned collagen scaffolds with CBD‐CBD‐NT‐3 and/or CBD‐BDNF modification were found to exhibit long‐term effects on axonal regeneration and remyelination in rodents and canines with completely transected SCI, through the anterograde tracing of BDA‐labeled CST axons and histochemical and transmission electron microscopy analysis. [ 65a,127a,128 ]…”

“…[ 132 ] Various functionalized scaffolds were prepared for the specific induction of NSC adhesion, migration, and differentiation into neurons to address deficiencies in the number of new neurons developed and the rapid diffusion of grafted cells under the SCI microenvironment. [ 69a,77,126c ]…”

“…[ 162 ] Thus, to better facilitate endogenous neurovascular regeneration and functional recovery after complete transection SCI, our group has developed a dual‐cue‐laden scaffold with both CBD‐SDF‐1α and Taxol‐loaded liposome modification. [ 77 ] The dual‐cue‐laden scaffold efficiently enhanced endothelial cell migration and improved vessel regeneration, and presented synergistic effects for the promotion of neurite outgrowth and descending and propriospinal axonal regeneration.…”

Bone Marrow Mesenchymal Stem Cell-Derived Exosome-Educated Macrophages Promote Functional Healing After Spinal Cord Injury

“…Therefore, an ideal restorative approach to enhancing long-term functional recovery after SCI should promote both postinjury axon growth and vascular perfusion in the injured region. A great number of methods have been developed as treatment options for SCI that promote angiogenesis coupled to axon growth ( Li X. et al, 2020 ; Liu et al, 2021 ).…”