Pre-Clinical Evaluation of CBD-NT3 Modified Collagen Scaffolds in Completely Spinal Cord Transected Non-Human Primates

Spinal cord injury (SCI) repair is one of the most desirable but extremely challenging clinical problems. Developing suitable animal models and validating the therapeutic interventions in these models is the prerequisite for SCI repair improvement. Non-human primates, closer to humans than other species, are considered to be ideal models for translating laboratory discoveries into human clinical trials. In this study, the acute thoracic (T9) complete transection model in rhesus monkeys was established to evaluate the effects of linear-ordered collagen scaffold (LOCS) and LOCS combined with collagen binding neurotrophin-3 (CBD-NT3), which has been demonstrated to promote axonal regrowth and functional restoration in rodent models. After 10 months post-surgery, the grafted groups dramatically reduced cystic cavity formation and chondroitin sulfate proteoglycans (CSPGs) deposition and facilitated the ingrowth of axonal fibers at the lesion site. Further, the grafted groups displayed more regenerated fibers, exhibiting remyelination and synapse formation. Notably, the LOCS+CBD-NT3 group showed significant locomotor and electrophysiological recovery compared with the Control and LOCS groups. Therefore, LOCS+CBD-NT3 transplantation represents an effective strategy to promote spinal cord repair in non-human primates. More importantly, this complete transection model in non-human primate will contribute to effectively evaluating the potential interventions and accelerating clinical transformation in the future.