Programmable Controlled-Release Bionic Spinal Cord Graft Promotes Repair and Functional Recovery after Spinal Cord Injury

The existing strategies for spinal cord injury (SCI) repair are restricted by the limitations of experimental models and intervention measures. Although the potential of stem cells, biomaterials, and electromagnetic stimulation has been demonstrated in animal models, their clinical translation has been relatively ineffective. In the present study, using the concepts of biomimetic neural tissue engineering to address the complex spatiotemporal characteristics of injured spinal cord repair, we created a programmable controlled-release bionic spinal cord graft with a topological scaffold composed of silk fibroin and collagen. By employing microfluidic drug-loaded microsphere technology and dual regulation by exosomes and extracellular matrix derived from human stem cells, the graft exhibited sustained release of neurotrophic factors, providing a beneficial regenerative microenvironment for SCI repair. In a mouse T10 3-mm hemisection SCI model, the graft facilitated tissue repair of the injured spinal cord, vascular remodeling, sensory and motor functional reconstruction, bladder function recovery, and the reversal of muscle atrophy. This study presents a new strategy for effective injured spinal cord repair using a programmable controlled-release bionic spinal cord graft, and the results suggest potential for application in humans for spinal cord repair and functional reconstruction.