Tissue-Engineering Approaches for Central and Peripheral Nervous-System Regeneration
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MRS BULLETIN/NOVEMBER 1996
sible for the integrity of the overall structure of a peripheral nerve. While the PNS shows regenerative capabilities, this is in general not the case for the CNS. The mechanisms explaining the poor regeneration capabilities of the CNS have started to be elucidated. The expression of inhibitory molecules in the mammalian-adult nervous system seems to be an essential component in the inherent lack of CNS regeneration. Examples for possible applications of materials systems addressing certain issues of PNS and CNS regeneration are presented in the following sections.
Peripheral-Nervous-System Nerve Regeneration In contrast to the CNS, adult mammalian peripheral nerves are capable of regeneration. Following a cut lesion, a sequence of events called Wallerian degeneration takes place. In the distal end—the end on the peripheral side— axons degenerate and Schwann cells eliminate myelin debris. Persisting basal-membrane tubes and Schwann cells serve as a substrate for regrowing axons from the proximal stump where the injury does not extend further back than to the next myelinated segment. There are two methodological approaches to nerve repair following cut injuries. The use of surgical methods have improved the outcome of surgical
nerve repair over the last decades, but functional recovery is rarely complete. The surgical methods following nerve injuries consist of epineurial suturing of cut nerve endings and the use of "biologic glue"—that is, fibrin glue for the reattachment of injured nerves or the application of CO2 lasers to weld the separated tissue. The main shortcoming of all the previously mentioned techniques is that they are no longer applicable to large nerve defects. Application of a tensile force is deleterious to regeneration and prevents closure of large nerve gaps. Autologous nerve grafts—nerves that are taken from the patient—are typically used to bridge large nerve gaps. The grafts are typically harvested from sensory nerves of the patient's leg and sutured between both nerve stumps to bridge the existing gap. An alternative technique that uses so-called nerve guidance channels is being investigated. Nerve guidance channels are tubular conduits fabricated out of a variety of polymeric materials such as silicone elastomer, poly(vinyl chloride) (PVC), acrylonitrile vinylchloride copolymer (PAN-PVC), poly(glycolic acid) (PGA), poly-L-lactic acid (PLLA), polytetrafluoroethylene (PTFE), or collagen. Both nerve endings are sutured to the open ends of the channel. By virtue of the proximal stump's inherent capability to regenerate, its axons will extend toward the distal nerve segment on the other side of the channel. The channels provide general guidance for regenerating neurons and prevent ingrowth of deleterious scar tissue. In experimental rodent models, these prostheses allow peripheral-nervous tissue regeneration up to a gap distance of 10 mm. Present investigations concentrate on the positive alteration of the regenerative environment via biochemical or physical methods t
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