If the injury is a clean-cut injury without contusion, the standard of care is to perform an end-to-end epineural repair (Fig. 3.3). The first goal of the epineural repair is coaptation of the nerves without tension [24, 25]. Because the bone has often been shortened to facilitate replantation, primary repair without tension is usually not difficult. The second goal is to reduce the formation of regeneration inducing scar tissue (see above). This is achieved by the epineural placement of sutures, performing minimal intraneural dissection, and using as few stitches as necessary to perform the repair. While the number of sutures needed to coapt a nerve is far smaller than what is needed, for example, in the arterial repair, it depends partly on the nerve being repaired. Four to eight simple interrupted sutures are used to approximate the two ends [12]. For digital nerves, usually three stitches are adequate and for larger nerves more stitches might be necessary. Nerve repair should be performed using an operative microscope for two reasons. First, the operative microscope aids in carefully placing stitches in the epineurium only, thus reducing the internal scar tissue which impedes regeneration, and secondly, magnification significantly aids in identifying the superficial vessels that are visible along the longitudinal aspects of the nerve segments (vasa nervorum). Aligning these vessels is an excellent method for the alignment of the fascicles, which significantly reduces misdirected axonal regeneration [26]. While it is not our preferred method, some groups have successfully performed sutureless epineural repair using fibrin glue [27].

Epineural sleeve repair is a variation of epineural repair that is used when there is some contusion associated with the tips of the transected nerve stump (Fig. 3.4). The repair calls for peeling back the epineural sheath on the distal nerve stump and trimming back the contused fascicles by 2 mm. The fascicles are aligned using cues from the vasa nervorum, and the distal epineural sleeve is then sutured to the proximal sleeve. This repair is potentially advantageous compared to standard epineural repair, because it moves the suture lines away from the regenerating fascicular ends. There are no clinical comparisons that have proven significant statistical advantage of this variation to standard epineural repair methods [26].

Nerve ends can also be coapted using fascicular or grouped fascicular repair (Fig. 3.5). In this case, the individual fascicles are aligned using perineural sutures, or groups of fascicles are aligned using sutures within the internal epineurium. Even though the technique provides superior fascicular alignment, it requires the use of at least two sutures per fascicle, which causes intraneural scar development and the reduction of blood flow that can worsen the final result. The method has fallen out of favor because clinical studies show no advantages of this technique over epineural suturing [26]. For nerves that are partially injured, however, there might still be a role for limited fascicular repair.

If one of the severed nerve segments is not available for coaptation, an end-to-side repair can be performed. The evidence on the overall clinical outcome is highly variable. Some of the variability in the outcome is related to the lack of a clear understanding of how axons from the donor nerve pass into distal segment, thus begging the need for further inquiry both in the laboratory and in the clinical setting [28]. Recent evidence comparing end-to-side repair with conventional (end-to-end) repair techniques indicates that end-to-side repair have functionally inferior outcome and should be used only as salvage procedures [29].

When direct repair of a transected nerve is not possible, a nerve graft, nerve conduit, or nerve transfer needs to be considered in order to achieve functional restoration. The gold standard of reconstructing a nerve gap is with a nerve autograft. Autografts provide resident Schwann cells as well as the microarchitecture necessary to guide sprouting axons. Some of the candidates for autograft harvest include sural nerve (30–50 cm), dorsal cutaneous branch of the ulnar nerve (4–6 cm), superficial branch of the radial nerve (20–30 cm), lateral antebrachial cutaneous nerve (10–12 cm), and the medial antebrachial cutaneous nerve (10–12 cm). Autograft harvest, while imperative in some cases, should be used cautiously as it can lead to significant donor site morbidity, which includes hypesthesia at the donor site, increased neuroma formation in the donor nerve, and (usually) a separate incision [12].

It is our preference to use the sural nerve for autograft as it is a relatively easy harvest site, can be harvested by a separate team while the recipient site is being prepared, and results in relatively minimal donor site morbidity. On the other end of the spectrum, using the sensory branch of the radial nerve should be avoided at all costs as numbness and parasthesias associated with its harvest can be devastating to the patient. In selecting a nerve for autografting, several principles should be followed. First, size is important. Larger grafts can lead to central neural necrosis, and increased scar tissue formation, which can impede regeneration. Secondly, sensory nerve autografts containing small diameter fibers can lead to mediocre functional outcome due to the mismatch of size. Thirdly, a risk-benefit analysis should be performed for each donor site and the one with the least morbidity should be selected. Since there are limited options for autografts, research has been carried out to better understand the potential of biological and artificial conduits to fill nerve defects [31].

Given the limited options of nerve autografts as well as the well-known morbidity in using them, multiple candidate materials for biological nerve conduits have been explored including arteries, veins, skeletal muscle, and epineurium. Veins have also been successfully used as inside-out or turn-over grafts. The collagen, laminin, and Schwann cells, which are found on the adventitia of veins, contribute to the increased speed of axonal regeneration found in turn-over vein grafts when compared to standard vein grafts [32]. Combination biological grafts containing vein, filled with skeletal muscle, have been found to be useful in filling nerve gaps ranging from 0.5 to 6 cm. Skeletal muscle tissue contains longitudinally oriented basal lamina which facilitates contact adhesion of migrating Schwann cells and ingrowing axonal fibers. Additionally filling the vein with muscle prevents the graft from collapsing [31]. Tendon grafts, which have similar longitudinal microarchitecture, have also been shown to be effective nerve conduits [33]. Epineural grafts are derived from neural tissue and produce large amounts of laminin B2 and VEGF, which augments Schwann cell attachment and axonal growth. Furthermore, epineural grafts are less immunogenic than the other biological conduit materials and could therefore even serve as an effective allograft. [26] It is our preference, when there is a limitation of nerve autograft or when the risks of harvest outweighs the benefits, to use turn-over vein grafts as they are relatively easy to harvest, are in abundant supply, and can usually easily be found in the same surgical field as the nerve that is being repaired (e.g., in forearm for cases of digital nerve reconstruction).

Artificial nerve conduits were initially made of flexible, non-immunogenic but nonbiodegradable materials such as silicone and PTFE. Silicone conduits tend to develop a capsule of circumferentially oriented smooth muscle myofibroblasts, which constricts the conduit and the growing nerve segment [34]. Morbidities caused by the scarring and constriction of ten requires reoperation for removal of these conduits. Furthermore, silicone is nonpermeable and does not allow the exchange of larger biomolecules that may be beneficial to the growing axon [15]. Given the limitation of these early artificial conduits, newer conduit materials have been utilized including synthetic biodegradable materials such as aliphatic polyesters and polyphosphoesters as well as naturally occurring biodegradable materials such as collagen, hyaluronic acid, and fibrin. Aliphatic polyesters include various biodegradable non-immunogenic polymers such as polyglycolic acid (PGA), poly-(lactic acid) (PLA), polycaprolactone (PCL), poly-lactide-coglycolide (PLGA) copolymer, poly-(L-lactic acid) (PLLA), and poly-(3-hydroxybutyric acid) (PHB) [15]. PGA is a commonly used material in sutures and mesh. It is broken down by hydrolysis within 90 days. PGA tubes are commercially marketed to bridge sensory nerve gaps less than 30 mm (Neurotube, Synovis Life Technologies Inc., USA). The copolymerization process used to synthesize aliphatic polyesters such as PLGA and PLLA can be altered to vary degradation times, thermal properties, mechanical performance, and wettability of these materials. The permeability of these materials which is important to maintain the nutrient exchange and as well as growth factor leakage from the conduits can also be adjusted by adjusting the crystallinity of these synthetic materials [31].