The three major types of autografts are trunk grafts, cable grafts, and vascularized nerve grafts [3]. Trunk grafts are mixed motor and sensory grafts. Trunk grafts have poor functional results due to their instability and large diameters which inhibits its ability to properly revascularize the center of the graft. Cable grafts are several sections of small nerve grafts aligned in parallel to connect fascicular groups. Vascularized nerve grafts have the advantage that there is no period of ischemia compared to nonvascularized grafts and the necessity for revascularization is avoided [3]. Sensory donor nerves are most often used, with the sural nerve being the most commonly harvested (Fig. 7.1a, b). The choice of autograft is dependent on several factors, that is, the size of the nerve gap, location of proposed nerve repair, and associated donor-site morbidity [8]. Use of autografts is currently restricted to critical nerve gaps of nearly 5 cm length [6].

The main limitations in the use of nerve autografts are considered to be mismatch of donor nerve size and fascicular inconsistency between the autograft and the distal/proximal stumps of the recipient nerve. Because a mismatch in axonal size and alignment further limits the regeneration capacity of the autografts, the type of nerve autografts chosen, like motor nerves, sensory nerves, or mixed nerves, is also decisive for a successful outcome [6]. A prolonged surgical time together with the potential risk of infection and formation of painful neuroma represents other important drawbacks of nerve autografting [6]. Altogether, the recovery time for the patient can be prolonged, owing to the need for a second surgery. The limitations of autografts forced researchers to develop alternative manufacturing approaches for novel nerve conduits for peripheral nerve repair [6].

Nerve allografts have demonstrated clinical utility in repairing extensive peripheral nerve injuries where there is a paucity of donor nerve material. Allografts used in peripheral nerve injuries are commercially processed to be cell- and protein-free [3]. This allows the nerve allograft to serve as a scaffold that is repopulated by Schwann cells and host axons over time [3]. The use of allografts presents limitations including especially risk of cross contamination, immune rejection, secondary infection, and limited supply [6]. Therefore, the use of allografts requires systemic immunosuppressive therapy, but long-term immune suppression is not a desirable treatment due to increased risk of infection and decrease of healing rate, and it occasionally results in tumor formation and other systemic effects [6]. In order to overcome some of these limitations, nerve allografts can be processed by repeated irradiation, freeze–thaw cycles, and decellularization with detergents [11].

Since 2007, decellularized nerve grafts are in clinical use. Since 2013, this alternative is also available in German-speaking countries; however, only a few clinics in Germany gathered experience in this field (Fig. 7.2).

The allogeneic transplants, which are generated from human donor nerve, combine many advantages due to its macrostructure and the three-dimensional microstructure. First clinical observations indicated in broken sensitive nerves good results to a defect distance of 3 cm. In the ten cases described, the 2-point discrimination (2PD) was 6 mm or better.

The largest prospective study on the use of allogeneic nerve grafts was published in 2011 by Brooks et al. under the name “RANGER study.” The RANGER study registry was initiated in 2007 to study the use of processed nerve allografts (AxoGen^® nerve allograft (AxoGen Inc., Alachua, FL)) in contemporary clinical practice [12]. Twelve sites with 25 surgeons contributed data from 132 individual nerve injuries. Data was analyzed to determine the safety and efficacy of the nerve allograft. Sufficient data for efficacy analysis were reported in 76 injuries (49 sensory, 18 mixed, and 9 motor nerves). The mean age was 41 ± 17 (18–86) years. The mean graft length was 22 ± 11 (5–50) mm. Subgroup analysis was performed to determine the relationship to factors known to influence outcomes of nerve repair such as nerve type, gap length, patient age, time to repair, age of injury, and mechanism of injury. Meaningful recovery was reported in 87% of the repairs reporting quantitative data. No graft-related adverse experiences were reported, and a 5% revision rate was observed. Processed nerve allografts performed well and were found to be safe and effective in sensory, mixed, and motor nerve defects between 5 and 50 mm. The outcomes for safety and meaningful recovery observed in this study compare favorably to those reported in the literature for nerve autograft and are higher than those reported for nerve conduits.

Another research team used acellular nerve xenografts and seeded them with bone marrow stromal cells [14]. When the allograft and the xenograft were compared with electrophysiological studies, it was observed that the xenografts were as effective as the allografts in regenerating the nerves. Allograft and xenografts have certain disadvantages such as disease transmission and immunogenicity.