Appropriate Scaffold Selection for CNS Tissue Engineering

Abstract

Cellular transplantation, due to the low regenerative capacity of the Central Nervous System (CNS), is one of the promising strategies in the treatment of neurodegenerative diseases. The design and application of scaffolds mimicking the CNS extracellular matrix features (biochemical, bioelectrical, and biomechanical), which affect the cellular fate, are important to achieve proper efficiency in cell survival, proliferation, and differentiation as well as integration with the surrounding tissue. Different studies on natural materials demonstrated that hydrogels made from natural materials mimic the extracellular matrix and supply microenvironment for cell adhesion and proliferation. The design and development of cellular microstructures suitable for neural tissue engineering purposes require a comprehensive knowledge of neuroscience, cell biology, nanotechnology, polymers, mechanobiology, and biochemistry. In this review, an attempt was made to investigate this multidisciplinary field and its multifactorial effects on the CNS microenvironment. Many strategies have been used to simulate extrinsic cues, which can improve cellular behavior toward neural lineage. In this study, parallel and align, soft and injectable, conductive, and bioprinting scaffolds were reviewed which have indicated some successes in the field. Among different systems, three-Dimensional (3D) bioprinting is a powerful, highly modifiable, and highly precise strategy, which has a high architectural similarity to tissue structure and is able to construct controllable tissue models. 3D bioprinting scaffolds induce cell attachment, proliferation, and differentiation and promote the diffusion of nutrients. This method provides exceptional versatility in cell positioning that is very suitable for the complex Extracellular Matrix (ECM) of the nervous system.

Keywords: Bioprinting; Cell differentiation; Extracellular matrix; Neurodegenerative diseases; Tissue engineering.

Figure 1.

The lobes of the human cerebral cortex (lateral view) and some functional regions of the cerebrum.

Figure 2.

Electrical action potential in the nerve cells.

Figure 3.

The structure and operation of available bioprinting methods: A) Inkjet printing method: In this method, air pressure pulses or mechanical pulses are used to eject the hydrogels/droplets. B) Microextrusion printing method: It uses the pneumatic, piston- and screw-based mechanisms to supply a continuous flow of bio-inks. C) Laser-guided direct cell printing method: This method influences the difference in refractive indices of cells, culture media to trap and assist them onto a receiving substrate. D) Laser-induced direct cell printing method: The vapor bubble is created by the laser and results in the removal of the hydrogel droplets from the absorbing layer.