The spatial arrangement of cells in a 3D-printed biomimetic spinal cord promotes directional differentiation and repairs the motor function after spinal cord injury

Spinal cord injury is a permanent destructive disease that causes devastating neurologic deficits and disability. Long-term complications are associated with low prognosis, mortality, and decreased quality of life. The functional recovery depends on the regeneration of neurons and the growth of medullated axons. Single treatment strategies, including cell transplantation, cannot adapt to a changeable microenvironment. Patients with spinal cord injuries need more effective, long-term, and stable treatment options. Therefore, we investigated the benefit of a combined-tissue engineering strategy by loading homologous bone mesenchymal stem cells (BMSCs) and Schwann cells in three-dimensional (3D) scaffolds. We placed BMSCs and Rat Schwann cells (RSCs) in specific spatial arrangements using cell gravity and the diffusion effect to promote the formation of intercellular connections and cell-directed differentiation. This novel bioengineering system allowed us to control multiple factors, including cell types, cell relative position, and axon growth direction in the scaffold. Our system facilitated motor function recovery by enhancing tissue mimicry and allowing the reconstruction of medullated axons. This new 3D-integrated printing platform is multi-function and can simulate biomimetic tissue using different types of materials and multi-cells scaffolds. We believe that this study can help promote the clinical development and application of 3D printing in the field of regenerative medicine.