The central nervous system (CNS) comprises the brain and spinal cord, and controls the vital functions of the human body. Degeneration of the CNS, caused by neurological diseases or physical damages, leads to losses of neuronal cell bodies such as axons and neurons. This degeneration has shown to be a condition very challenging to reverse since the CNS has a low capacity to replace neurons. Despite many promising therapeutic strategies having been explored in animal models, there is still no known effective cure for CNS degeneration, such as injuries in the spinal cord. 1 2
Spinal cord injury (SCI) is a severe CNS traumatic disease that partially or completely hampers sensorial and locomotor functions and is characterized by loss of neural cells, axonal rupture and demyelination. 1
Figure 1: The central nervous system. 3
Recent advances in tissue engineering and nanotechnology promoted practical strategies to repair spinal cord injuries through the combination of neural stem cells and biomaterials. Neural tissue engineering focuses on providing an appropriate microenvironment for cells to promote the regeneration of functional neurons, thereby establishing effective connections between them across the injured area and restoring conductive nerve function. 4
For a successful nerve regeneration, physical support must be provided as a 3D structure that, when associated with neural stem cells, can improve host tissue engraftment and enhance the development of new tissues to facilitate cell function.4
Joung et al. (2018) created a platform to manufacture a spinal cord scaffold through extrusion-based multi-material 3D bioprinting. Using this approach, the researchers were able to place induced pluripotent stem cells derived from spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells in precise positions within 3D printed biocompatible scaffolds during assembly. Bioprinted sNPCs were able to differentiate and extend axons along the scaffold channels on a microscale. The activity of these neuronal networks was confirmed by physiological spontaneous calcium flow studies. The combination of cells and biomaterial proposed in this work can direct the reconstruction of functional axonal connections in areas of tissue damage in the central nervous system; therefore, it could be used as a therapeutic agent for chronic spinal cord injury to regenerate axons throughout the injury site. 5
Figure 2: The 3D printed spinal cord developed by Joung et al. (2018). 5
Another strategy to treat spinal cord injuries was studied by Liu et al. (2021). The team developed a biocompatible bioink composed of functional chitosan, hyaluronic acid derivatives, and Matrigel®. The manufactured scaffold maintained high neural stem cell viability and provided a benign microenvironment that facilitated cell-material interactions and neuronal differentiation for optimal neural network formation. In vivo experiments with rat models indicated that the bioprinted scaffolds promoted axon regeneration and decreased glial scar deposition, leading to significant locomotor recovery. Thus, the study demonstrated the feasibility of neural stem cell-loaded scaffolds for spinal cord repair in vivo, representing a versatile strategy for precise engineering of the central nervous system. 1
REFERENCES
1. Liu, X. et al. 3D bioprinted neural tissue constructs for spinal cord injury repair. Biomaterials 272, 120771 (2021).
2. Koffler, J. et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat. Med. 25, 263–269 (2019).
4. Bedir, T., Ulag, S., Ustundag, C. B. & Gunduz, O. 3D bioprinting applications in neural tissue engineering for spinal cord injury repair. Mater. Sci. Eng. C Mater. Biol. Appl. 110, 110741 (2020).
5. Joung, D. et al. 3D Printed Stem-Cell Derived Neural Progenitors Generate Spinal Cord Scaffolds. Adv. Funct. Mater. 28, (2018).