page_title: Neural tissue engineering
section_title: Implantation of neural tissue developed in vitro
hierarchical_section_title: Neural tissue engineering / CNS / CNS treatments and research / Implantation of neural tissue developed in vitro
caption_attribution_description: English: Phase image of embryoid bodies (EBs) in suspension culture after 24 hours of formation. EBs were created from approximately 1000 mouse embryonic stem cells (D3 cell line). Scale bar = 100 µm.
context_page_description: Neural tissue engineering is a specific sub-field of tissue engineering. Neural tissue engineering is primarily a search for strategies to eliminate inflammation and fibrosis upon implantation of foreign substances. Often foreign substances in the form of grafts and scaffolds are implanted to promote nerve regeneration and to repair damage caused to nerves of both the central nervous system and peripheral nervous system by an injury.
context_section_description: A third method for treating CNS injuries is to artificially create tissue outside of the body to implant into the injury site. This method could treat injuries that consist of large cavities, where larger amounts of neural tissue needs to be replaced and regenerated. Neural tissue is grown in vitro with neural stem or progenitor cells in a 3D scaffold, forming embryoid bodies (EBs). These EBs consist of a sphere of stem cells, where the inner cells are undifferentiated neural cells, and the surrounding cells are increasingly more differentiated. 3D scaffolds are used to transplant tissue to the injury site and to make the appropriate interface between the artificial and the brain tissue. The scaffolds must be: biocompatible, biodegradable, fit injury site, similar to existing tissue in elasticity and stiffness, and support growing cells and tissues. The combination of using directed stem cells and scaffolds to support the neural cells and tissues increase the survival of the stem cells in the injury site, increasing the efficacy of the treatment.
  There are 6 different types of scaffolds that are being researched to use in this method for treating neural tissue injury:
  Liquid hydrogels are cross-linked hydrophobic polymer chains, and the neural stem cells are either grown on the surface of the gel or integrated into the gel during cross-linking of the polymer chains. The major drawback of liquid hydrogels is there is limited protection of the cells that are transplanted.
  Supportive scaffolds are made from solid bead-shaped or microporous structures, and can act as carriers for the transplanted cells or for the growth factors that the stem cells secrete when they are differentiating. The cells adhere to the surface of the matrix in 2D layers. The supportive scaffolds are easily transplanted into the brain injury site because of the scaffold size. They provide a matrix promoting cell adhesion and aggregation, thus increasing increased healthy cell culture.
  Aligning scaffolds can be silk-based, polysaccharide-based, or based on other materials such as a collagen-rich hydrogel. These gels are now enhanced with micro-patterns on the surface for the promotion of neuronal outgrowths. These scaffolds are primarily used for regeneration that needs to occur in a specific orientation, such as in spinal cord injuries.
  Integrative scaffolds are mainly used to protect the transplanted cells from mechanical forces that they are exposed to in the process of implantation into the site of the injury. These scaffolds also decrease the likelihood of having the inflammatory cells located at the site of the injury migrate into the scaffold with the stem cells. Blood vessels have been observed to grow through the scaffold, thus the scaffold and cells are being integrated into the host tissue.
  A combination of engineered scaffolds presents an option for a 3D scaffold that can have both the necessary patterns for cell adhesion and the flexibility to adapt to the ever changing environment at the injury site. Decellularized ECM scaffolds is an option for scaffolds because they more closely mimc the native tissue, but these scaffolds can only currently be harvested from amputations and cadavers.
  These 3D scaffolds can be fabricated using particulate leaching, gas foaming, fiber bonding, solvent casting, or electrospinning techniques; each technique creates a scaffold with different properties than the other techniques.
  Incorporation success of 3D scaffolds into the CNS has been shown to depend on the stage at which the cells have differentiated. Later stages provide a more efficient implantation, while earlier staged cells need to be exposed to factors that coerce the cells to differentiate and thus respond appropriately to the signals the cells will receive at the CNS injury site. Brain-derived neurotrophic factor is a potential co-factor to promote functional activation of ES cell-derived neurons into the CNS injury sites.
caption: Mouse Embryonic Stem Cells (mESCs) embryoid bodies (EBs)
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