Cavernous nerve regeneration using acellular nerve grafts.
BACKGROUND
The restoration of erectile function following complete transection of nerve tissue during surgery remains challenging. Recently, graft procedures using sural nerve grafts during radical prostatectomy have had favorable outcomes, and this has rekindled interest in the applications of neural repair in a urologic setting. Although nerve repair using autologous donor graft is the gold standard of treatment currently, donor nerve availability and the associated donor site morbidity remain a problem. In this study, we investigated whether an "off-the-shelf" acellular nerve graft would serve as a viable substitute. We examined the capacity of acellular nerve scaffolds to facilitate the regeneration of cavernous nerve in a rodent model.


METHODS
Acellular nerve matrices, processed from donor rat corporal nerves, were interposed across nerve gaps. A total of 80 adult male Sprague-Dawley rats were divided into four groups. A 0.5-cm segment of cavernosal nerve was excised bilaterally in three of the four groups. In the first group, acellular nerve segments were inserted bilaterally at the defect site. The second group underwent autologous genitofemoral nerve grafts at the same site, and the third group had no repair. The fourth group underwent a sham procedure. Serial cavernosal nerve function assessment was performed using electromyography (EMG) at 1 and 3 months following initial surgery. Histological and immunocytochemical analyses were performed to identify the extent of nerve regeneration.


RESULTS
Animals implanted with acellular nerve grafts demonstrated a significant recovery in erectile function when compared with the group that received no repair, both at 1 and 3 months. EMG of the acellular nerve grafts demonstrated adequate intracavernosal pressures by 3 months (87.6% of the normal non-injured nerves). Histologically, the retrieved regenerated nerve grafts demonstrated the presence of host cell infiltration within the nerve sheaths. Immunohistochemically, antibodies specific to axons and Schwann cells demonstrated an increase in nerve regeneration across the grafts over time. No organized nerve regeneration was observed when the cavernous nerve was not repaired.


CONCLUSIONS
These findings show that the use of nerve guidance channel systems allow for accelerated and precise cavernosal nerve regeneration. Acellular nerve grafts represent a viable alternative to fresh autologous grafts in a rodent model of erectile dysfunction.
Connolly
Stephen S
SS
Department of Urology, Wake Forest Institute for Regenerative Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Yoo
James J
JJ
Abouheba
Mohamed
M
Soker
Shay
S
McDougal
W Scott
WS
Atala
Anthony
A
D000818:Animals; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000209:etiology / Q000601:surgery*; D005109:Extracellular Matrix / Q000637:transplantation*; D005240:Feasibility Studies; D005267:Femoral Nerve / Q000637:transplantation; D006085:Graft Survival; D008297:Male; D009416:Nerve Regeneration; D010413:Penis / Q000294:innervation*; D011183:Postoperative Complications / Q000601:surgery; D011468:Prostatectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D014182:Transplantation, Autologous