An update–tissue engineered nerve grafts for the repair of peripheral nerve injuries

Introduction

Peripheral nerve injury (PNI) is a complex challenge due to its many etiologies and varying degrees of severity. Although the etiologies of PNI are vast, traumatic injuries, such as motor vehicle accidents and gunshot wounds, account for the majority of cases (Scholz et al., 2009). Approximately 360,000 people suffer a PNI in the United States annually, which amounts to an estimated annual expenditure of $150 billion healthcare dollars (Noble et al., 1998; Taylor et al., 2008). Moreover, patients are left with a spectrum of disability following PNI, ranging from mild sensorimotor dysfunction to the devastating loss of motor and/or sensory function.

The current approach to PNI repair depends on the degree of injury. If no gap exists in the transected nerve, a direct repair via an end-to-end neurorrhaphy can be performed by joining each perineurial defined fascicle (Siemionow and Brzezicki, 2009). In this technique, care must be taken to avoid tension, as this would diminish epineurial blood flow and risk tissue necrosis (Smith, 1966a, b; Lundborg and Rydevik, 1973). For gaps of 1 cm or less, either biological or synthetic nerve conduits have been used to approximate the nerve stumps and guide regeneration with good success (Meek and Coert, 2002; Battiston et al., 2009; Moore et al., 2009; Siemionow and Brzezicki, 2009). Although some authors have used synthetic nerve conduits for nerve gaps up to 2.5 cm, the complication rates have been high, including fistulization of the conduit requiring removal and tube extrusions (Chiriac et al., 2012; Safa and Buncke, 2016). Therefore, the current gold standard for repairing gaps greater than 1 cm is autologous nerve, which provides the native scaffolding of Schwann cells, extracellular matrix (ECM), and growth factors needed for optimal regeneration (Pfister et al., 2011).

The most common sources of autologous nerve include the sural nerve, medial antebrachial cutaneous nerve, and posterior interosseous nerves (Battiston et al., 2017). While harvesting sensory nerves results in the least of morbidity at the harvest site, using a sensory nerve autograft in a motor nerve or a mixed motor-sensory nerve injury can lead to poor functional outcomes (Rbia and Shin, 2017). In addition, despite the superior clinical efficacy of autografting, the supply of autologous nerve is limited and harvesting the nerve from an additional surgical...