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Regeneration in an Enzyme-Treated Decellularized Nerve Allograft<br />

Institution where the work was prepared: Washington University School of Medicine, St. Louis, MO, USA<br />

Sami H. Tuffaha, BA; Daniel A. Hunter; Ying Yan; Janina P. Luciano; Susan E. Mackinnon; Gregory H. Borschel;<br />

Washington University in St. Louis<br />

INTRODUCTION:<br />

Peripheral nerve injuries are currently reconstructed using nerve autografts. The very limited supply of autologous nerve grafting material<br />

combined with the morbidity associated with nerve autograft harvest, such as sensory loss and painful neuroma <strong>for</strong>mation, necessitate<br />

a suitable substitute to autografting. AxoGenô nerve allografts are manufactured by decellularizing human nerves with a process<br />

that removes antigens and degrades molecules that inhibit neuroregeneration while leaving laminin intact. We designed a study to<br />

compare the neuroregenerative capacities of the AxoGenô nerve graft to those of an autograft and the NeuraGenô conduit (the leading<br />

hollow tube nerve conduit).<br />

METHODS:<br />

To obtain processed nerve grafts, sciatic nerves from Brown Norway rats were harvested and sent to AxoGenô <strong>for</strong> proprietary processing.<br />

Three groups (Avanceô, NeuraGenô and isograft) were im<strong>plan</strong>ted into the sciatic nerve of Lewis rats at two different lengths (14mm<br />

and 28mm). Grafts were harvested at either a 6 or 12 week endpoint and evaluated <strong>for</strong> neuroregeneration using histomorphometry.<br />

Retrograde labeling, motor endplate staining, walking track analysis, and wet muscle mass were used to analyze functional recovery.<br />

RESULTS:<br />

Midgraft histomorphometric data of the 14mm grafts at 6 weeks showed significantly greater regeneration in AxoGenô processed<br />

grafts, as compared to NeuraGenô conduits.† Fiber distribution patterns resembled those of an isograft as demonstrated by electron<br />

micrographs of midgraft sections.<br />

CONCLUSION:<br />

The AxoGenô grafts were well-tolerated by all animals. The 6 week histomorphometric data suggest that the neuroregenerative capacities<br />

of AxoGenô processed grafts are comparable to those of an isograft and significantly better than those of the leading biosynthetic<br />

conduit. Pending functional outcome measures and data from the 12 week endpoint, it appears that AxoGenô grafts could provide<br />

a much needed substitute <strong>for</strong> autografts.<br />

Graft Type<br />

Total fiber number ±<br />

std dev<br />

Percent Nerve<br />

± std dev<br />

* or †: significant difference between groups; p < 0.05 by ANOVA.<br />

Fiber width (µm)<br />

± std dev<br />

120<br />

Nerve density<br />

(fibers/mm 2 )<br />

± std dev<br />

Isograft 13649 ± 4967*† 23.5 ± 11.0* 3.0 ± 0.2* 23191 ± 9616*<br />

AxoGen TM<br />

Processed<br />

Nerve Graft<br />

6041 ± 1515† 16.5 ± 3.4† 3.3 ± 0.2† 14749 ± 3512†<br />

NeuraGen TM 1427 ± 2018* 1.3 ± 1.8*† 1.6 ± 2.2*† 1278 ± 1821*†

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