NEURAL CONDUITS Why Neural Conduit Tubes?

Autograft: These grafts are taken primarily from the treated patient and have demonstrated a success rate of only 50 per cent on patients treated . The use of autograft also requires secondary removal of degenerated axons and myelin by the host from the graft itself, increasing the healing time. Similarly in recent studies, it has been shown that sensory and motor neurons have different Schwann cell (SC) modalities and if placed in the incorrect microenvironment, may limit their regenerative ability. Autograft use is currently limited to a critical nerve gap of approximately 5 cm in length and beyond this distance requires the use of allograft. Allograft: It requires the use of extensive immune suppression up to 18 months post implantation, and patients become susceptible to opportunistic infections, occasionally resulting in tumour formation. Use of tubes (Neural guides) for brain injury therapy A nerve guidance conduit (also referred to as an artificial nerve conduit or artificial nerve graft) is an artificial means of guiding axonal regrowth to facilitate nerve regeneration and is one of several clinical treatments for nerve injuries. The nerve guidance channels provide a conduit for the diffusion of growth factors and reduce the glial scar formation. 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. 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. There is a potential use of autologous Schwann cells that aid in CNS regeneration. This novel approach enhances axonal regeneration. This may be due to the fact that Schwann cells are the myelinating glial cells in the PNS and are known to play a key role in CNS regeneration. Schwann cells promote neural regeneration and remyelination by secreting adhesion molecules L1 and neural cell adhesion molecule (N-CAM), extracellular molecules (collagen and laminin) and a number of tropic factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). So, the general sequence of regeneration within the silicone nerve guides is as follows: After implantation of autologous Schwann cells, fluid and cytokines (including neurotrophic factors) primarily generated by the Schwann cells build up within the nerve guide. Within 7 days an oriented fibrin scaffold is formed and cells primarily fibroblasts penetrate into the nerve guide while axon debris is removed by Schwann cells and macrophages in the distal end. From 7 to 14 days, regenerating axons and Schwann cells penetrate into the nerve guide using the newly formed fibrin scaffold as a substrate. Schwann cells in the distal component begin to form part of

the Bands of Bngner long cellular tracts from the severed distal nerve ending to the final muscular targets. Between 14 and 56 days, Schwann cells myelinate the regenerating axons that exit the nerve guide, directed by the Bands of Bngner in the distal nerve stump to their targets.

Sequence of events in empty silicone nerve guides. Initially, fluid and cytokines fill up the nerve guide (a), followed by the formation of a fibrin matrix inside the lumen which initially supports invading fibroblasts (blue) (b), followed by Schwann cells (green) and axons (red) (c), which eventually penetrate to the distal stump. The regenerated nerve usually is thinner in the middle of the bridge(yellow).