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Silk-silk Conduits Filled With Native Spider Silk Fibers Successfully Promoted Nerve Regeneration In A 10 Mm Sciatic Nerve Defect In Rats
Lorenz Semmler, MD1, Aida Naghilou Naghilou, PhD1, Flavia Millesi, MSc1, Sonja Wolf, -1, Anda Mann, BSc1, Eva Györi, MD PhD1, Fritz Vollrath, PhD2, Tamara Weiss, PhD1, Christine Radtke, MD1.
1Medical University of Vienna, Vienna, Austria, 2University of Oxford, Oxford, United Kingdom.

PURPOSE: The surgical repair of nerve transection injuries remains a challenging task and often results in unsatisfactory functional recovery. If a direct coaptation is not possible, the current gold-standard is the use of an autograft. However, the availability of autologous nerve tissue is limited and the harvest of a donor nerve entails functional loss and possible donor site morbidity. In the search for alternatives, different synthetic and biological materials are currently tested to bridge nerve gaps. Recent studies supported silk as promising material for tissue engineering and the development of artificial nerve conduits. In addition, nerve conduits that contain an internal framework as guiding structures could enhance a directed axonal re-growth. Spider silk possess excellent mechanical properties such as an adequate tensile strength, long-term degradability and a non-immunogenic nature, which support their use as promising conduit filling material. In this study, we investigated the performance of a silk fibroin-based conduit filled with spider silk fibers to bridge a 10 mm sciatic nerve defect in rats.
METHODS:
In 18 male Sprague-Dawley rats, a 10 mm piece of the sciatic nerve was resected and immediately bridged with 1) autografts (control group, n=6), 2) empty silk conduits (experimental group one, n=6), and 3) silk conduits filled with spider silk fibers (experimental group two, n=6). Walking track analysis was performed for each animal prior to surgical intervention and every 14 days over a course of 14 weeks. Functional recovery was evaluated by calculating the sciatic functional index (SFI) according Bain et al. At the endpoint, animals were sacrificed and the nerves were harvested to assess axon re-growth and myelination by histomorphometric as well as immunofluorescence analyses on paraffin sections. RESULTS:
The walking track results showed that there was no statistical difference in the mean SFI of animals treated with the autograft or the silk fiber containing silk conduits. Moreover, the immunofluoresence stainings of nerve sections illustrated a similar pattern of regenerated nerve tissue in sections of autografts and filled silk conduits, while a less advanced nerve regrowth was seen in the samples containing empty silk conduits. The histomorphometric parameters displayed a similar number of myelinated axons in the autografts and filled silk conduits. Additionally, the mean axon area was comparable between the autograft and the silk conduit filled with spider silk. However, the mean myelin area was the largest in the autograft group. CONCLUSION:
Taken together, our study demonstrated that the functional recovery of a 10 mm sciatic nerve defect bridged with silk conduits containing spider silk fibers as internal guiding structure was comparable to and autologous nerve grafts.


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