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 (CNS) and peripheral nervous system (PNS) by an injury.
Introduction
The nervous system is divided into two sections: the CNS and the PNS. The CNS consists of the brain and the spinal cord, while the PNS consists of nerves that originate from the brain and spinal cord and innervate the rest of the body.
The need for neural tissue engineering arises from the difficulty of the nerve cells and neural tissues to regenerate on their own after neural damage has occurred. The PNS has some, but limited, regeneration of neural cells. Adult stem cell neurogenesis in the CNS has been found to occur in the hippocampus, the subventricular zone (SVZ), and spinal cord. CNS injuries can be caused by stroke, neurodegenerative disorders, trauma, or encephalopathy. A few methods currently being investigated to treat CNS injuries are: implanting stem cells directly into the injury site, delivering morphogens to the injury site, or growing neural tissue in vitro with neural stem or progenitor cells in a 3D scaffold. Proposed use of electrospun polymeric fibrous scaffolds for neural repair substrates dates back to at least 1986 in a NIH SBIR application from Simon. For the PNS, a severed nerve can be reconnected and reinnervated using grafts or guidance of the existing nerve through a channel.
Recent research into creating miniature cortexes, known as corticopoiesis, and brain models, known as cerebral organoids, are techniques that could further the field of neural tissue regeneration. The native cortical progenitors in corticopoiesis are neural tissues that could be effectively embedded into the brain. Cerebral organoids are 3D human pluripotent stem cells developed into sections of the brain cortex, showing that there is a potential to isolate and develop certain neural tissues using neural progenitors.
Another situation that calls for implanting of foreign tissue is use of recording electrodes. Chronic Electrode Implants are a tool being used in research applications to record signals from regions of the cerebral cortex. Research into the stimulation of PNS neurons in patients with paralysis and prosthetics could further the knowledge of reinnervation of neural tissue in both the PNS and the CNS. This research is capable of making one difficult aspect of neural tissue engineering, functional innervation of neural tissue, more manageable.
CNS
Causes of CNS injury
There are three main causes of CNS injury: stroke, traumatic brain injury (TBI), or developmental complications. Strokes are classified as either hemorrhagic (when a vessel is damaged to the point of bleeding into the brain) or ischemic (when a clot blocks the blood flow through the vessel in the brain). When a hemorrhage occurs, blood seeps into the surrounding tissue, resulting in tissue death, while ischemic hemorrhages result in a lack of blood flow to certain tissues. Traumatic brain injury is caused by external forces impacting the cranium or the spinal cord. Problems with CNS development results in abnormal tissue growth during development, thus decreasing the function of the CNS.
CNS treatments and research
Implantation of stem cells to the injury site
One method to treat CNS injury involves culturing stem cells in vitro and implanting the non-directed stem cells into the brain injury site. Implanting stem cells directly into the injury site prevents glial scar formation and promotes neurogenesis originating from the patient, but also runs the risk of tumor development, inflammation, and migration of the stem cells out of the injury location. Tumorigenesis can occur due to the uncontrolled nature of the stem cell differentiation, inflammation can occur due to rejection of the implanted cells by the host cells, and the highly migratory nature of stem cells results in the cells moving away from the injury site, thus not having the desired effect on the injury site. Other concerns of neural tissue engineering include establishing safe sources of stem cells and getting reproducible results from treatment to treatment.