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

Abstract

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.

A decellularized spinal cord extracellular matrix-gel/GelMA hydrogel three-dimensional composite scaffold promotes recovery from spinal cord injury via synergism with human menstrual blood-derived stem cells

“…With the advancement of regenerative medicine technology, functional scaffold materials combined with stem cell transplantation have played invaluable roles in treating SCIs. [9][10][11] Functional scaffold materials not only created a microenvironment suitable for the growth, differentiation and nerve regeneration of stem cells, 12 but also built a bridge to provide support and guidance for the regrowth of damaged nerves in the injury site. 13 The decellularized extracellular matrix (dECM) was a biological scaffold derived from tissues, whose cellular components had been removed, while retaining the structural components and functional ECM proteins.…”

Biomaterial-Based Schwann Cell Transplantation and Schwann Cell-Derived Biomaterials for Nerve Regeneration

“…Wang et al fabricated a bio-ink by mixing 10% GelMA solution with rat SCs and BMSCs, then underwent extrusion-based bioprinting to construct a bionic spinal cord stent. By changing the cellular components in the GelMA-based bioink, different spatial arrangement of SCs and BMSCs was achieved that facilitated motor function recovery after spinal cord injury (Wang et al, 2021 ).…”

“…Bi-printing provides unique advantages in precise design and controlling the cellular distribution in the 3D scaffolds to mimic the native tissues or to meet special requirements. Wang et al encapsulated BMSCs and SCs in two different GelMA-based bioinks, then bioprinted 3D scaffolds with spatial arrangement of the cells, respectively (Wang et al, 2021 ). Compared to the homogeneous hydrogel encapsulated with both cells, the 3D-printed scaffold with spatial distribution resulted in better functional recovery after spinal cord injury.…”

Application and progress of three‐dimensional bioprinting in spinal cord injury

“…In a more recent study by Jianhao et al, homologous bone mesenchymal stem cells and SCs were placed in specific spaces and loaded into 3D scaffolds using cell gravity and diffusion effects to study the advantages of combined tissue engineering. Results indicate that this 3D integrated printing process can enable different types of materials and cells to simulate bionic tissues, as well as promote the recovery of motor function by strengthening tissue simulation to reconstruct myelinated axons 77 …”

“…Results indicate that this 3D integrated printing process can enable different types of materials and cells to simulate bionic tissues, as well as promote the recovery of motor function by strengthening tissue simulation to reconstruct myelinated axons. 77 To sum up, multicellular printing in neural tissue engineering can simulate the tissue structure of the central nervous system, which can be used to create new bionic scaffolds, and which is more conducive to the reconstruction of axon connection and repair of damaged central nervous systems. These studies open new directions for developing treatments for nervous system disorders.…”