Advocates of fibrin glue-assisted nerve repair note that fibrin glue is atraumatic, quick, and easy to apply. If fibrin glue drips in between the nerve interface, it will not block regenerating axons [19]. Even though nerve repair should be considered an off-label use (commercially available fibrin glue does not have Food and Drug Administration approval for this application), a recent survey indicates that many surgeons incorporate it into their repair strategy [20]. Animal data where fibrin glue is used instead of microsuture repair in general indicates a similar efficacy though intermittent reports of complete nerve dehiscence are concerning [21–29]. The nerve repair is weakest within the first 2 weeks, and studies comparing load to gap and load to failure have shown fibrin glue is inferior to suture repair in the first 2 weeks but similar thereafter [30–32]. Alternatively, fibrin glue can be used to augment suture repair, allowing fewer sutures to be used, which was shown to have similar functional outcomes but less scarring and better axonal alignment [33]. A biomechanical cadaver study demonstrated effective resistance to gapping but no significant augmentation of actual holding strength over minimal suture coaptation [34]. While there are no published clinical outcomes studies, fibrin glue augmentation does appear to be useful at least to control gapping and maintain fascicular alignment when used in addition to standard suture repair.

Autologous fibrin glue can be prepared in the operating room using the patient’s own blood (to be mixed with pooled blood bank thrombin) though this does not appear to be as effective as commercially available product [34]. Commercially available fibrin glue comes as two separate syringes containing different components of the clotting cascade. The syringes are depressed simultaneously (either using a double syringe holding bracket or by coordinated effort), and as the contents of the two syringes mix at the application site, a gel-like clot is formed. A piece of Esmarch or similar material placed behind approximated nerve ends (typically following at least partial suture neurorrhaphy) can act as a temporary mold to shape the gel as it is applied so that an adhesive cylinder forms around the coaptation site. The gel is firm enough to augment the repair after about 3 min. Commercially available fibrin glue should be used with caution in patients with aprotinin sensitivity.

Nerve connectors are simply conduits applied over approximated or nearly approximated nerve ends. Any biologic or commercially available nerve tube can be trimmed and applied in this capacity although currently one product is specifically marketed for this purpose. The many potential advantages of this technique include the creation of a concentrated neurogenic milieu within the protected microenvironment at the enclosed coaptation site, the blockage of escaping axons, and a barrier to invading scar tissue [35, 36]. There is some evidence that the small gap between the nerve ends may encourage end-organ specificity in which axons self-direct to the appropriate target (though this is typically felt to be a limited process at best) [37]. With fewer microsutures required to maintain the coaptation, the theoretical harmful effects of “suture trauma” and foreign material reaction can be blunted and at least partially shifted away from the regenerating axons. The anchoring sutures at the connector ends can redistribute tension, which has been shown in animal models to improve nerve regeneration by allowing maximal angiogenesis at the repair site. In a rat model, Schmidhammer demonstrated that splinting the nerve repair by suturing the distal silicone tube to the nerve epineurium 3 mm distal to the tube, thereby relieving tension at the nerve repair site, led to the highest rate of angiogenesis and nerve function recovery [38]. Perhaps most importantly, the enveloping connector seems to direct and align the nerve fascicles which may be especially helpful with multifascicular nerves such as the median nerve at the wrist.

Added cost and lack of proven (as opposed to theoretical) benefit are the primary disadvantages of incorporating nerve connectors into a median nerve repair, though several clinical reports on “conduit repairs” of larger peripheral nerves involve such small gaps that they could be considered connector-assisted repairs. In a randomized control trial, Lundborg found similar outcomes at both short- and long-term (5-year) follow-up on silicone tube repairs versus suture repairs of median and ulnar nerves at the wrist or distal forearm across gaps of only 3–5 mm [39, 40]. Another randomized study comparing collagen conduits (bridging gaps of 6 mm) to suture repair of median or ulnar nerves in the distal forearm showed no difference in outcomes after 24 months [41].

Currently, only one commercially available nerve connector is available (AxoGuard Nerve Connector, AxoGen, Inc., Alachua, FL). It is manufactured using tissue-engineered acellular porcine small intestine submucosa and can be applied in a variety of ways. Though pre-soaking has been recommended by the manufacturer to soften the product, implantation in the dry and rigid state facilitates passage of the nerve stump into the short tube. Once positioned, either the natural moisture within the body or normal saline irrigation will soften the material enough to allow suture passage. Nerve stumps can be pulled into the connectors using horizontal or “U” stitches placed through the end of the connector, through the outer epineurium, and back through the connector similarly to more conventional nerve conduit application. As the suture is pulled snug, the nerve stump can be guided into the tube though this can be an exercise in frustration without at least a semiskilled assistant. If using the more popular 10 mm long connectors (it is also available in a 15 mm length), the sutures should be placed 2–2.5 mm from the end of the connector and 2–2.5 mm from the end of the nerve so that once secured, about 4–5 mm of nerve stump will be held within the tube. When repeated with the second nerve stump, the nerves should be ideally just barely touching. A perfectly sized tube (they come in a variety of diameters, and picking the correct size can be challenging) will hold the fascicles in end-to-end alignment. If the connector is too big, the “slack” can be taken out of the side by pinching the excess material and fastening with hemoclips or sutures (Fig. 27.4). Alternatively, the nerve stumps can be inserted into the tube and held in place with two or three simple stiches placed through the end of the connector and the underlying epineurium. This technique can work well when the nerve is stiff, such as larger diameter nerves like the median nerve, and the repair is completely tension free as in acute injuries with generous mobilization.

Nerve connector can also be combined with epineurial sutures to consistently control rotational and longitudinal fascicular alignment. One of the nerve stumps is inserted into the connector which is slipped completely over the end of the stump and onto the nerve trunk. The nerve ends are lined up, and a few simple epineurial stitches are placed so that the ends are barely touching. The connector is then slid back over the neurorrhaphy site so that the inner surface of the tube molds the nerve ends to further enhance end-to-end approximation. Simple sutures placed at the end of the connector relieve tension at the nerve face and reinforce the repair.

Any biotolerant tubular structure can theoretically be used as a nerve conduit if nerve stumps can be inserted into and secured within the ends. In fact, some surgeons routinely use local veins to bridge defects in small caliber nerves [42]. However, in an effort to improve surgical efficiency and avoid “donor” morbidity, most conduit nerve repairs are performed using one of several commercially available versions.

In addition to the practical advantages of speed and convenience, the principle advantages of conduit repair are similar to those discussed regarding nerve connectors. Conduit application is technically straightforward, and the protected microenvironment established between the nerve stumps contains concentrated neurotrophic factors. The main difference between connectors and conduits is that a fibrin clot must form between the separated nerve stumps to act as a biological scaffold supporting Schwann cell migration and subsequent axon elongation across the nerve gap [43]. In other words, if the fibrin clot does not form, nerve regeneration will not occur. Commercially available nerve conduits are made of one of three materials: polyglycolic acid, collagen, or polycaprolactone. All share the common characteristics in that they are semirigid, to resist collapse and kinking; semipermeable, to allow diffusion of oxygen and nutrients to support nerve regeneration; and absorbable, to avoid long-term irritation.

In the right circumstances, conduits have an established track record. Conduits consistently support the formation of nerve regenerate across a 1 cm defect in rodent sciatic nerves [44]. Human data is more variable with several studies supporting nerve regeneration in small caliber nerves across short defects. Rinker et al. reported sensory recovery after repair of digital nerves with gaps averaging 9 mm [42]. Similarly, Taras et al. and Haug et al. reported good results for digital nerve repairs for gaps averaging 12 and even 19 mm [45, 46]. On the other hand, Battiston et al. had only 4/19 good or excellent results using similar criteria as other published studies [47], and Lohmeyer reported no recovery in defects greater than 15 mm [48].

The fibrin clot formation essential for successful nerve regeneration becomes less stable and therefore less predictable with longer gaps and larger diameter nerves. Moore et al. reported on four failed conduit major nerve repairs [49], and Chiriac et al. reported a satisfactory recovery in only 1 out of 12 conduit major peripheral nerve repairs [50]. Both recommended against conduit repair of major peripheral nerves. With gaps more than a few millimeters, therefore, conduits would not be considered a reliable way to repair the median nerve trunk but could be considered for gaps up to a couple of centimeters in the terminal branches.

Frequently, especially with endoscopic or mini-incision carpal tunnel releases, the injury to the median nerve is not immediately recognized. Even if complaints at the first postoperative visit prompt an urgent re-exploration, this delay of only 10–14 days is enough to allow nerve retraction and early fibrosis. Most frequently, the delay is much longer to allow a suspected neuropraxia to resolve, or the surgeon adopts a defensive “wait-and-see” attitude. Fairly rapidly, fibrosis of the retracted nerve makes mobilization more difficult, and end bulb neuromas develop, requiring nerve resection at the time of repair. Adequate resection of scarred and neuromatous nerve tissue and avoidance of excessive tension at the repair site are essential for successful nerve regeneration so that the gap between nerve ends (or between sections of the nerve if only partially cut) demands some form of bridging construct. Current options include conduits, nerve autograft , or acellular nerve allograft . As stated in the previous section, the indication for conduit repair of the median nerve is very limited and is not practical for delayed repairs where a significant gap exists.

Processed human nerve allograft (PNA) offers many of the advantages as conduits regarding off-the-shelf convenience and avoidance of donor morbidity associated with autograft harvest. The bioengineering process that renders the allograft immunotolerant by necessity removes all cells (including Schwann cells ) but maintains much of the internal architecture of normal nerve tissue. This architecture acts as the scaffold to support migrating Schwann cells necessary to support axon elongation across the graft. Some guidance cues such as laminin and growth factors such as brain-derived growth factors are also retained by the allograft nerve tissue to further enhance the neurosupportive environment. The only commercially available processed acellular nerve allograft product (Avance, Axogen, Inc., Alachua, FL) incorporates an additional enzymatic removal of chondroitin sulfate proteoglycans. Chondroitin sulfate proteoglycans inhibit axon regeneration, and treated allograft in experimental models supports superior axon regeneration compared to untreated allograft [51]. Gamma irradiation sterilizes the tissue without significantly altering the infrastructure.