An aptamer-based bionic spinal cord scaffold elicits robust neurogenesis in situ after spinal cord injury in rats
Transected spinal cord injury (SCI) results in significant structural disruption of the spinal cord. The reconstruction of neural pathways following SCI faces several key challenges, including inadequate endogenous neural stem cells (NSCs) and poor neurogenesis in natural repair process, and concerns related to the long-term survival of neurons following exogenous transplantation. In the current study, we report an oligonucleotide aptamer drug (Apt19S) which is first proven to recruit endogenous NSCs to the site of injury following SCI, and therefore develop a bionic spinal cord scaffold that can sustainedly release Apt19S and neurotrophin-3 (NT-3) to provide the neurogenic niche with the necessary mechanical properties and support for in situ spinal cord repair. The bionic scaffold successfully recruited a significant number of endogenous NSCs in vivo and established a neurogenic niche that was abundant in NT-3, thereby promoting neuronal differentiation and the formation of neuronal networks Regenerated nerve fibers including 5-hydroxytryptamine-positive nerve fibers and corticospinal tract grew robustly into the injury site and generated synaptic connections with the newborn neurons. Collectively, our findings indicate that our aptamer-based bionic spinal cord scaffold elicits a robust neurogenesis process in situ, breaking the limitations imposed by poor self-repair ability in the adult spinal cord. Overall design: Six adult female SD rats (220–250 g, supplied by the Experimental Animal Center of Sun Yat-sen University) were randomly divided into two groups: 1) Apt19S-decellularized optic nerve (A-DON) scaffold implant. 2) decellularized optic nerve scaffold implant. (n=3 for each group).Two weeks after SCI, three rats were selected from each of the DON and A-DON groups for mRNA sequencing in the spinal cord.