Application of a Porcine SIS Nerve Cap for Prevention of Neuromas and Associated Pain
Shahryar Tork, MD1; Jennifer Faleris, BS2; Anne Engemann, PhD2; Erick DeVinney, BS2; Ian L. Valerio, MD, MS, MBA1; (1)Department of Plastic Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, (2)AxoGen, Alachua, FL
Following traumatic or oncologic nerve amputations, 20% of patients will develop painful neuromas resulting from aberrant axonal regeneration. Previous studies suggest that isolation of the nerve end within a cap following primary amputations and neuroma revisions may prevent or reduce neuroma pain. This study investigated the efficacy of a novel porcine small intestine submucosa (SIS) nerve cap to prevent a pain response in an established rodent tibial nerve neuroma transposition model (TNT).
Fifty-seven (57) Sprague-Dawley rats were evaluated using the TNT model. Tibial nerves were ligated, transected, and trans-positioned to the lateral aspect of the hindlimb. The nerve stumps were either treated with a nerve cap containing spiral chambering (NCs), a Nerve Cap containing a center partition (NCp) or an Open Tube (OT). Surgical Control (SC) nerve stumps remained untreated. All trans-positioned nerves were secured subcutaneously with a single ligation suture. Weekly pain response testing was conducted by mechanically stimulating each nerve end trans-dermally using a calibrated von Frey monofilament and observing the animal for hindlimb withdrawal or vocalization. The animals were euthanized at 8 and 12 weeks. Tissues were explanted, embedded, sectioned longitudinally, and stained with Neurofilament 200. Quantitative measurements of axon density were obtained using image analysis of optical density (OD) within the nerve stump.
At 8 weeks the pain response was statistically higher in the SC group compared to the NCs group (p=0.01). At 12 weeks the pain response in the SC group was statistically higher than all other groups (p<0.05). Conversely, at 8 and 12 weeks, the SC group showed statistically lower OD of neurites extending within the samples compared to all other groups, NCs, NCp, and OT (p<0.001). Given the inverse relationship between axon density and collagen, the decrease in OD measure is indicative of increased collagen deposition and associated neuroma formation.
Decrease in OD measurements at the site of a regenerating nerve stump is associated with increased collagen deposition and disorganized axonal outgrowth, features that signify neuroma formation. The investigational porcine SIS nerve cap effectively reduced behavioral pain responses and increased optical density of the regenerating nerve stump predicting a reduced likelihood of painful neuroma formation. Future application of the nerve cap in the treatment residual limb patients may provide relief from symptomatic neuromas, thus improving an amputee's tolerance of his or her prosthetic while also decreasing the incidence of painful neuromas.
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