No Difference in Outcomes Detected Between Decellular Nerve Allograft and Cable Autograft in Rat Sciatic Nerve Defects

Abstract

Background: Nerve injuries with a gap/defect represent a clinical challenge without a clear solution. Reconstruction with cable autografts is a common treatment technique, and repair with decellular nerve allograft is a newer option. The purpose of this study was to compare the functional outcomes of reconstruction with cable autografts with those of matched-diameter decellular nerve allografts to evaluate the relative importance of diameter as well as the autograft-versus-allograft nature of the reconstruction. Methods: A unilateral 10-mm sciatic nerve defect was created in 81 genetically identical male Lewis rats and then repaired with a reverse autograft, 4 or 5 sural nerve cable autografts, or a matched-diameter decellular nerve allograft. In each group, at each time point (12, 16, and 20 weeks), all 9 animals underwent functional testing and 5 of the 9 underwent histologic analysis. Functional testing included bilateral measurements of the isometric tetanic force of the tibialis anterior (primary outcome), the weight of the tibialis anterior, and the gastrocnemius compound muscle action potential (CMAP) latency. Histologic evaluation included an axon count as well as measurement of the axon density, fiber diameter, myelin thickness, and G-ratio. Results: The repair groups did not differ significantly in terms of isometric tetanic force, muscle weight, or CMAP latency, but these measurements did differ significantly according to the time after surgery (p < 0.05). The isometric tetanic force percent recovery (width of the 95% confidence interval) for the reverse autograft, cable autograft, and decellular nerve allograft was 57.7% (15.6%), 57.0% (23.4%), and 56.0% (19.7%), respectively, at 12 weeks; 69.1% (14.7%), 65.6% (18.5%), and 65.9% (29.1%) at 16 weeks; and 72.5% (18.2%), 73.7% (25.6%), and 71.8% (22.4%) at 20 weeks. Isometric tetanic force and muscle weight recovery were greater and CMAP latency was shorter at 20 and 16 weeks after surgery than they were at 12 weeks. The treatment type did not affect any of the histologic outcomes. Conclusions: In this animal study, we found that matched-diameter decellular nerve allograft was not significantly different from reverse autograft or cable graft reconstruction in terms of function and histologic outcomes. These findings support decellular nerve allograft as a viable treatment option for nerve reconstruction. Clinical Relevance: This study showed that decellular nerve allograft was no different from cable or reverse autograft in terms of outcome measures in a rat sciatic nerve defect model. If these results are applicable clinically, it would obviate the need for autograft nerve harvest and its ensuing donor site morbidity.

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

“…The reverse-polarity autograft is not the clinical gold standard; however, we were unable to use sural autograft due to the aforementioned limitations and chose to use the reverse-polarity autograft, which is the predominant positive control used in both small animal and large animal nerve defect studies (46,(70)(71)(72). Furthermore, Tang et al (73) recently demonstrated that there was no significant difference in performance of the sural nerve autograft versus reverse-polarity nerve autograft in a rat sciatic nerve defect model, further justifying the use of the reverse-polarity autograft as a clinical control.…”

Procedure Costs of Peripheral Nerve Graft Reconstruction

“…This is consistent with the clinical literature, given the potential for increased OR time and the need for a harvest site for autograft nerve repair procedures. 5,11,14 There was no significant difference in mean R&B cost between autograft and allograft nerve repair procedures with average costs directionally lower, although not statistically significant, for allograft nerve repairs. The Lans et al study reported lower total costs of care for allograft versus autograft repair in the inpatient setting ($25,751 and $29,560 respectively) and similar costs for allograft versus autograft repair in outpatient settings ($13,143 and $12,635, respectively) from an analysis of the 2018 Medicare Standard Analytic File.…”

“…Introduced into clinical practice in 2007, nerve allograft includes the potential for reduced operative time, avoiding additional risks associated with the donor site (such as neuroma formation or infection), the use of regional rather than general anesthesia, 11,12 and off-the-shelf availability (in 15 mm to 70 mm length, and 1-2 mm to 4-5 mm diameter), contributing to ease of use. 12,14,15 In a published meta-analysis comparing meaningful recovery rates and postoperative complications after autograft, allograft, and conduit repair in nerve gaps greater than 5 mm and less than 70 mm, overall meaningful recovery for sensory and motor function was not significantly different between autograft and allograft across both short and long gaps. Meaningful recovery rates for autograft (81.6%) and allograft (87.1%) repairs were significantly higher compared with conduits (62.2%) in sensory short gap repairs (nerve gaps 5-30 mm).…”

“…11,[14][15][16] However, use of this surgical technique can result in complications/sequelae at the donor nerve site, including cold intolerance, dysesthesias, sensory loss, neuroma formation, chronic nerve pain, infection, and scarring, and can be constrained when repairing extensive injuries due to a limited supply of donor nerve. 5,11,12,14,15,17,18 Nerve allograft has been shown to be an acceptable alternative to nerve autograft. Introduced into clinical practice in 2007, nerve allograft includes the potential for reduced operative time, avoiding additional risks associated with the donor site (such as neuroma formation or infection), the use of regional rather than general anesthesia, 11,12 and off-the-shelf availability (in 15 mm to 70 mm length, and 1-2 mm to 4-5 mm diameter), contributing to ease of use.…”

Surgical Angiogenesis of Decellularized Nerve Allografts Improves Early Functional Recovery in a Rat Sciatic Nerve Defect Model

“…42,43 This study and others have demonstrated that isometric tetanic force is a reliable technique in determining the degree of functional recovery of a reinnervated muscle as a direct measure of reinnervation. 5,[44][45][46] Electrophysiologic outcomes tended to be superior in the allograft wrapped in superficial inferior epigastric artery fascial flap group compared to nerve allograft alone. As compound muscle action potential is greatly affected by factors such as changes in temperature and electrode location, there is greater variability than isometric tetanic force data.…”