Nerve Lengthening as a Strategy for Nerve Repair
Holly M. Howarth, BS1; Adarsh Kadoor, BS1; Rayeheh Salem, MD1; Elisabeth Orozco, BS1; Mary Esparza, BS1; Sameer B. Shah, PhD2,3
1UCSD, La Jolla, CA, 2Orthopedic surgery, UCSD, San Diego, CA, 3VA San Diego Healthcare System, San Diego, CA
Background: Functional recovery is often poor for individuals with peripheral nerve injuries, especially for more severe injuries or for delayed repairs. For small nerve gaps, an end-to-end repair is preferred, even under slight tension. Autologous or synthetic grafts/conduits are used to bridge larger gaps, to eliminate tension at the site of repair. However, because axons must grow into, through, and out of the graft to reach their targeted end organs, the efficiency of regeneration and functional recovery may be impaired. Building on data that tensile loading accelerates the growth of axons, we propose the implantation of a new device that will gradually lengthen the proximal nerve stump towards the distal stump, to allow for an end-to-end repair.
Methods: A 10mm gap was created in the sciatic nerve of Lewis rats. In the autograft (gold standard) group (n=8), the transected nerve segment was reversed and sutured to the proximal and distal stumps. Rats recovered for twelve weeks. In the experimental (device) group (n=8), the proximal stump was secured to the lengthening device, and the nerve was stretched 1 mm/day for two weeks using an extracorporeal actuator. The device was then removed, nerve ends trimmed, and an end-to-end repair was performed. Rats recovered for ten more weeks. Sciatic Functional Index (SFI) and clawing (contracture) phenotypes were used to assess functional recovery. Immunolabeling was used to examine structural regeneration.
Results: In both groups, SFI improved over time after surgery, though not to pre-operative levels. While there was no significant difference in SFI between the device and autograft groups, there was significant improvement between two and eight weeks in the device group (p < .0001) but not the autograft group (p < .2316), suggesting improved recovery with nerve lengthening. Also, rats in the autograft group were more likely to display a contracture, consistent with significantly shorter paw length in autograft group vs. device (p<0.05). Axon counts distal to the repair site were significantly higher (p<0.05) and axons more evenly distributed across the nerve cross-section in device compared to autograft.
Discussion: Nerve lengthening followed by end-to-end repair resulted in equal or better functional improvement compared to autografts. Likelihood of contracture was also reduced in lengthened and repaired nerves, possibly due to more and/or more evenly distributed axons into tibial and peroneal branches of the sciatic nerve. Nerve lengthening followed by end-to-end repair offers a viable and potentially powerful strategy to repair large-gap nerve injuries.
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