The nervous system is a complex network structure, whose physiology comprises of several layers that help it in accomplishing its task. In some cases, these nerves are protected by the skull or vertebral columns, but in others, they lack this protection. Regardless of the location of the nerves, they need barriers that shield them from external factors that could affect their functioning by maintaining the homeostasis of their environment (Liu, Wang, and Yi 1). The complex nature of the nervous system has presented researchers with many challenges, especially when dealing with injuries to this system. This paper studies the engineering of neural tissue. However, it is not possible to focus on this area without prior knowledge of the structure of the nervous system. Therefore, this section describes the general anatomical structures of this system, which comprises the nervous system, spinal cord, and peripheral nervous system. After focusing on this area, the section will discuss the clinical treatment strategies used by bioengineers to repair nerves that have injuries.
Structure of the Nervous System
The nervous system is divided into two main sections called the Peripheral Nervous System (PNS) and the Central Nervous System (CNS). Moreover, these two sections also have other sub-divisions, with the CNS consisting of the spinal cord and the brain. The PNS has a motor (efferent) and sensory (afferent) neurons. Furthermore, the motor neurons are divided into somatic and Automatic Nervous System (ANS), which is again divided into the enteric, sympathetic, parasympathetic, and enteric sections (Schmidt and Leach 294). Each of these parts of the nervous system has particular work that cannot be done by a different one. Moreover, they are all complex in nature, which means that if one gets an injury, it affects a person substantially until it regenerates. However, given their complex structure, their regeneration is usually not easy, and in some cases, it does not happen (Schmidt and Leach 294). Therefore, bioengineering is normally used to help them regenerate, even though this process is complicated.
Cellular Components of the Nervous System
The main building blocks of the nervous system are two basic units, namely glial cells and neurons, which are specialized cells that transmit and receive chemical and electrical signals. The main work of the glial cells is supporting the neurons, which are a crucial part of the system. These cells have dendrites and axons that make up the soma and its extensions, which are in Figure 1 below. The group of the sensory nerve soma situated to the periphery of the spinal column is called the ganglion. The work of the dendrites is to transmit electrical signals to the cell body of the neurons, while axons conduct these impulses away (Liu, Wang and Yi 2). These Axons are grouped into nerve fascicles and nerve bundles.
Peripheral nerves have three protective connective sheaths that include the endoneurium, epineurium, and perineurium. The outer-most layer is the epineurium, and it has a dense tissue component, which encloses the entire nerve tissue. It encloses the peripheral nerves, fascicles, lymphocytes, blood vessels, and fibroblasts. The middle layer is the perineurium, and it wraps around each nerve fascicle (Liu, Wang, and Yi 2). This layer is made up of seven or eight concentric layers. This section is elastic due to its structure since it has myoepithelial cells that have epithelioid and myofibroblastoid features, such as a junction, which allow it to contract and extend. This ability makes it resistant to mechanical damage (Liu, Wang, and Yi 2). Finally, the innermost layer is the endoneurium, and it surrounds s a cluster of small nerve fibers, the myelin sheath.
The glial cells comprise the Schwann cells in the PNS, the astrocytes, which are found in the CNS, and the oligodendrocytes. Unlike the neurons, glial cells are in large numbers, and they have less ability to experience cell division, which affects their ability to undergo mitosis. In the PNS, all axons have a sheath encirclement that comprises of living Schwann cells. They have a basement membrane that bears a resemblance to that of the epithelial layers in the outer surface of the Schwann cells. However, axons in the CNS do not have this continuous basement membrane and sheath of the Schwann cells. Several axons form the myelin sheath, where they are encircled in the cell membrane of the Schwann cells. This myelin sheath is crucial for the axons since it improves the breeding velocity of impulses in the nerves. Figure 2 below shows the nerves in the PNS.
The endoneurium contains oriented collagen fibers, and it surrounds the Schwann cells' sheath and axons. The epineurium is a nerve system that comprises of thick bright red or yellow fibers, while the perineurium has thin pale greenish fibers (Romero-Ortega 25). Conversely, the spinal cord is a network that has external and internal anatomy that exists in a cylinder of gray and white matter. Its other parts are the dendrites, axons, and cell bodies. The gray matter is the spinal cord's core, and it has blood vessels, excitatory neurons, and glial cells (Ganau, Zewude, and Fehlings 4). The spinal cord also needs protection, and it gets it from the bony vertebrae, spinal meninges, cerebrospinal fluid, and adipose tissue. It also gets it from the gray matter, which contains axons and glial cells that protect and insulate the spinal cord. Figure 4 below shows an image of the anatomy of the spinal cord.
Furthermore, oligodendrocytes have the role of aiding the myelinating of the axons in the CNS. The astrocytes act as a blood-nerve barrier that creates three portions of the CNS, which are microglia, which are also called immune cells, blood proteins, and cells (Silver, Schwab, and Popovich 1). The white matter consists of fascicles, which are on the outer part of the spinal cord's bone, where it protects the PNS-CNS interface area (Ganau, Zewude, and Fehlings 6). This spinal cord contains a well-defined transition zone where the glial cells are separated.
Peripheral Nervous System Injury
The peripheral nerves link the spinal cord and the brain, and they are also in other parts of the body. Despite being fragile, these nerves play an essential role in the lives of a person. A fatal injury that can occur to these nerves is a complete cut-off. Such an injury is called peripheral neuropathy, and it separates the metabolic resources of the nerve cell bodies from the protease activity, which affects the functionality of the brain. This separation causes the distal portion of the PNS to start to regenerate, and it makes the cytoskeleton break down as its cell membranes dissolve. This process has small damaging effects, and it makes the proximal end of the nerve to swell. Besides, this degradation causes Schwan cells to cover axons in a circular form that causes the distal end to release cytokines, which improves the growth of the axon, and it also eliminates the myelin and axonal waste.
This removal of the wastes causes the nerve to repair itself, and it causes the nerve to start regenerating towards the distal stump, making the axon to start developing at the Ranvier nodes (Tezcan 4). While these nerves can heal and regenerate on their own, the process takes a long time since the rate is between two and five millimeters per day. Consequently, it causes the complete healing of a nerve to take many years, which calls for external regeneration of the nerves. This external regeneration uses a hollow nerve conduit that helps in the repair of peripheral nerves. When an injury occurs, a fibrin bridge forms at the gap and connects the entire injured part, which allows the usual regeneration of the nerve. Conversely, if the nerve conduit does not form, the fibrin bridge does not develop, causing the repair and regeneration to fail.
Central Nervous System Injury
Unlike in the PNS, axons in the CNS do not regenerate after an injury. The CNS contains a native extracellular environment that contains glycoproteins and myelin, which hinder the regeneration of the axons (Silver, Schwab, and Popovich 1). After an injury, macrophages enter the injured region, making the removal of inhibitory myelin to occur at a significantly slower rate, unlike in the PNS, where this process occurs at a fast rate. Infiltration of the macrophages starts after their recruitment, which depends on some factors, such as the unregulated cell adhesion molecules (Silver, Schwab, and Popovich 10). Moreover, before the recruitment of these cells starts, astrocytes spread in the injured area. Comparing the processes that occur after an injury in the PNS and CNS shows a significant difference.
Current Clinical Methods of Treating Nerve Injuries
Technological advancements have made it possible to deal with problems in more efficient methods than it was possible previously. However, damage to the PNS or CNS is still challenging for clinicians, even with the current technologies (Kubiak, Kung, and Brown 702). Despite this current state, developing techniques, such as tissue engineering, electroconductive conduits, neural stimulation, fat grafting, optogenetics, and cell-based therapies, provide hope for the future (Kubiak, Kung, and Brown 705; Tezcan 26). Specifically, these advancements increase the efficiency of regeneration of these nerves, thus, making them heal faster. Moreover, ongoing research on these technologies will lead to their improvement.
Challenges and Bioengineering Strategies for Nerve Repair
As already stated, nerve repair faces some challenges. The major ones are that it needs two surgeries that involve deleting tissue from a patient. Another issue is that the process demands an alternative to the autologous nerve graft. Moreover, clinical, functional recovery from these autologous nerve grafts do not always have a success rate of 100% (Tezcan 25).
Historical Introduction to Guidance Therapies
The physical guidance of an axon is essential among the various components of nerve repair. This guidance has significantly changed over time. For instance, for the 19th century, the recommended method was using fat sheath, metal and bone tubes, and autologous nerve grafts in the regeneration process of injured peripheral nerves. While some of these techniques are still in application currently, other microsurgical procedures emerged in the 1960s. These additions were the work of Millesi, and they provided a method of orienting these nerve fascicles towards the nerve end more efficiently, leading to better functional outcomes. Currently, the most recent technology for engineering repair of nerves is the autologous nerve graft (Tezcan 25). Now, while this is the latest technology, other more improved methods are in development. An excellent example is the use of scaffolds to enhance the regeneration of these nerves in the system.
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