A nerve guidance conduit (also referred to as an artificial nerve conduit or artificial nerve graft, as opposed to an autograft) is an artificial means of guiding axonal regrowth to facilitate nerve regeneration and is one of several clinical treatments for nerve injuries. When direct suturing of the two stumps of a severed nerve cannot be accomplished without tension, the standard clinical treatment for peripheral nerve injuries is autologous nerve grafting. Due to the limited availability of donor tissue and functional recovery in autologous nerve grafting, neural tissue engineering research has focused on the development of bioartificial nerve guidance conduits as an alternative treatment, especially for large defects. Similar techniques are also being explored for nerve repair in the spinal cord but nerve regeneration in the central nervous system poses a greater challenge because its axons do not regenerate appreciably in their native environment.
The creation of artificial conduits is also known as entubulation because the nerve ends and intervening gap are enclosed within a tube composed of biological or synthetic materials. Whether the conduit is in the form of a biologic tube, synthetic tube or tissue-engineered conduit, it should facilitate neurotropic and neurotrophic communication between the proximal and distal ends of the nerve gap, block external inhibitory factors, and provide a physical guidance for axonal regrowth. The most basic objective of a nerve guidance conduit is to combine physical, chemical, and biological cues under conditions that will foster tissue formation.
Materials that have been used to make biologic tubes include blood vessels and skeletal muscles, while nonabsorbable and bioabsorbable synthetic tubes have been made from silicone and polyglycolide respectively. Tissue-engineered nerve guidance conduits are a combination of many elements: scaffold structure, scaffold material, cellular therapies, neurotrophic factors and biomimetic materials. The choice of which physical, chemical and biological cues to use is based on the properties of the nerve environment, which is critical in creating the most desirable environment for axon regeneration. The factors that control material selection include biocompatibility, biodegradability, mechanical integrity, controllability during nerve growth, implantation and sterilization.
Scaffold topography
In tissue engineering, the three main levels of scaffold structure are considered to be: the superstructure, the overall shape of the scaffold; the microstructure, the cellular level structure of the surface; and the nanostructure, the subcellular level structure of the surface.
Superstructure
The superstructure of a conduit or scaffold is important for simulating in vivo conditions for nerve tissue formation. The extracellular matrix, which is mainly responsible for directing tissue growth and formation, has a complex superstructure created by many interwoven fibrous molecules. Ways of forming artificial superstructure include the use of thermo-responsive hydrogels, longitudinally oriented channels, longitudinally oriented fibers, stretch-grown axons, and nanofibrous scaffolds.
Thermo-responsive hydrogels
In traumatic brain injury (TBI), a series of damaging events is initiated that lead to cell death and overall dysfunction, which cause the formation of an irregularly-shaped lesion cavity. The resulting cavity causes many problems for tissue-engineered scaffolds because invasive implantation is required, and often the scaffold does not conform to the cavity shape. In order to get around these difficulties, thermo-responsive hydrogels have been engineered to undergo solution-gelation (sol-gel) transitions, which are caused by differences in room and physiological temperatures, to facilitate implantation through in situ gelation and conformation to cavity shape caused, allowing them to be injected in a minimally invasively manner.