*3.4. Necrosis*

Sensory nerves generally have a smaller diameter than the mixed sensory/motor nerves they are commonly used to repair. Often, multiple small diameter grafts are used so that the final diameter of the grafts approximates that of the nerve to be repaired. However, smaller diameter grafts are correlated with less functional recovery than larger diameter grafts [53–55]. This is ascribed to the lack of vascularization leading to necrosis of the Schwann cells within the graft [54,56]. Necrosis reduces, if not blocks, axon regeneration through the graft. This situation is not improved when multiple small grafts are used. To avoid necrosis, the best approach is to use vascularized nerve grafts (see the following section on vascularized grafts and inducing vascularization).

#### *3.5. Decreasing Recovery with Increasing Gap Length*

Sensory nerve grafts promote good to excellent functional recovery only when nerve gaps are <2 cm in length [57–59]. The extent of recovery decreases to only good for gaps ≥ 3 cm in length [60,61], decreases further for gaps up to 4 cm [58,62,63], and there is a precipitous decrease in recovery for gaps > 4–5 cm [58,64,65]. Few axons regenerate across grafts of 8 cm in length [57,60] and there are no reports of axons regenerating across gaps >10 cm in length [7,58,63,65–67]. Thus, neurological recovery decreases with increasing gap length [53]. Therefore, sensory nerve grafts are only considered reliable for "short" nerve gaps (≤3 cm) [55,68]. Furthermore, no material is Food and Drug Administration (FDA)-approved for repairing nerve gaps >3 cm in length [55,69,70].

The reduction in axon regeneration across long nerve grafts appears correlated with the longer time required to vascularize longer grafts [71]. As mentioned above, without vascularization, the graft environment is ischemic, which inhibits axon regeneration [72].

#### *3.6. Decreasing Recovery with Increasing Time between Nerve Injury and Repair*

Anastomosing nerve stumps of non-traumatic transected radial nerves of young males (25 years) immediately [73] or within 14 days [7] of the injury generally results in good neurological recovery for 67% of subjects [73]. However, as the delay in performing the repair increases, the recovery of good function decreases to 30%, fair in 28%, and fails for 42% of patients [7,73].

Similarly, when short nerve gaps are repaired using sensory nerve grafts, recovery is very good to excellent following repairs performed ≤ 14 days post-trauma [7] or good to excellent for repairs performed ≤ 2 months post-trauma [74]. However, the extent of recovery decreases significantly for repairs performed > 3 months post-trauma [62,75,76]. Thus, delays of >2 months result in good recovery in only 49% of patients [62], but are poor for repairs performed > 6 months post-trauma [62,77–79]. No recovery is reported for repairs performed > 10 months post-trauma [80,81].
