Tissue-engineered Peripheral Nerve

Nerve injuries occur by a variety of mechanisms, including traumatic wounds, thermal or chemical damage, myelin or axonal degeneration, and acute compression. These injuries typically result in the loss of motor function, sensory function, or both. Functional recovery is regained upon complete axonal regeneration, which includes remyelination and reinnervation (i.e., synapse formation) of the appropriate muscle and sensory targets. For severing injuries, the two nerve cable ends can be surgically reconnected if the repair does not put tension on the nerve cable. For gaps longer than B5 mm, an autologous nerve graft (i.e., autograft) from the patient’s own body is used to bridge the injury site. The most common donor nerves implemented clinically are the sural nerve and the medial and lateral antebrachial cutaneous nerves (1–3). Nerve autografts are, however, associated with several disadvantages: sensory loss as well as possible scarring and painful neuroma formation at the donor site, potential mismatches in diameter or length to the injured nerve, and the required multiple surgeries (4,5). Nerve allografts transplanted from other individuals are one potential alternative to autografts, but they require the use of immunosuppressants to reduce the patient’s response to transplant tissue antigens (6). These disadvantages associated with current clinical treatments have motivated the investigation of new approaches, such as tissue engineering, for addressing nerve injuries. The ultimate goal of peripheral nerve tissue engineering is to provide rationally designed alternatives to grafted tissue through a deeper understanding of the dynamic three-dimensional interactions of peripheral neurons, glial cells, and their extracellular matrix environment. Tissue engineering principles can also be implemented to develop new in vitro model systems to study cellular behaviors associated with regenerating nerve tissue. This entry provides a survey of emerging tissue engineering technologies to treat peripheral nerve injuries and to investigate regeneration processes in vitro. Several recent review articles have also addressed peripheral nerve tissue engineering and regeneration (7–10); therefore, this work will primarily focus on literature published during 2000–2005 and will emphasize advancements that have demonstrated an improved ability to promote functional repair in vivo or control cell behavior in vitro. The reader is directed toward published review articles for information on other related topics such as the neurobiology of neuronal and glial cell response to injury (11); the delivery of support cells including glial cells (7), genetically modified cells (7), and stem cells (12); the delivery of growth factors, drugs, and DNA (7,13); and electrical devices for stimulating, processing, and recording nerve behavior (14).