Long nerve gaps limit the regenerative potential of bioartificial nerve conduits filled with Schwann cells

Article type: Research Article

Authors: Sinis, Nektarios | Schaller, Hans-Eberhard | Becker, Stephan Thomas | Schlosshauer, Burkhard | Doser, Michael | Roesner, Harald | Oberhoffner, Sven | Müller, Hans-Werner | Haerle, Max

Affiliations: Klinik für Hand-, Plastische-, Rekonstruktive- und Verbrennungschirurgie, Universität Tübingen, BG-Unfallklinik, Tübingen, Germany | Labor für Molekulare Neurobiologie, Neurologische Klinik der Universität Düsseldorf, Düsseldorf, Germany | Klinik für Mund-, Kiefer-, Gesichtschirurgie, Universität Kiel, Germany | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Reutlingen, Germany | Deutsches Zentrum für Biomaterialien und Organersatz, Denkendorf, Germany | Institut für Zoologie, Zell- und Entwicklungsneurobiologie, Universität Hohenheim, Stuttgart, Germany

Note: [] Corresponding author: Dr. Nektarios Sinis, Klinik für Hand-, Plastische-, Rekonstruktive und, Verbrennungschirurgie, Berufsgenossenschaftliche Unfallklinik, Schnarrenberg 95, D-72076 Tübingen, Germany. Tel.: +49 7071 606 0; Fax: +49 7071 606 1037; E-mail: nsinis@bgu-tuebingen.de

Abstract: Purpose: Recently we successfully used a conduit of ε-caprolactone-co-trimethylene carbonate filled with Schwann cells (SC) across a 20 mm gap in a rat median nerve. In this study we applied the tubes with SC across a 40 mm gap in order to analyse the regenerative potential of the tubes in long nerve defects. Methods: To augment the nerve defect a cross-chest procedure was used and the tubes were implanted with injected isogeneic SCs inside (group 3). Both ulnar nerves were used for a 40 mm autograft (group 2). For control group non-operated animals were used (group 1). The grasping test, histology (S-100, PAM), electrophysiology, and the muscle weight were used to assess regeneration. Results: After 12 months, grasping was seen only in three animals of group 3 (3.6 g [95% CI: 0 to 7.6 g]). However, in group 2 all rats had a partial functional regeneration (42.8 g [95% CI: 39.1 to 46.6 g]). The grasping force of the non-operated animals (group 1) was 240.9 g [95% CI: 237.2 to 244.7 g] at the time. Histology from group 3 confirmed an irregular arrangement of fibres in contrast to more organized structures in group 2. Electrophysiology in group 3 displayed potentials only in the three animals with functional regeneration. In group 2 all animals exhibited potentials. A significant decrease of muscle weight was observed in groups 2 and 3, most prominent in the latter. Conclusion: Regeneration was not successful across the 40 mm gap using the applied tube in combination with SC. For future experiments further consideration should be taken in optimizing the cellular and material components that are critical for a successful application to overcome very large nerve gaps.

Keywords: Schwann cells, nerve conduit, nerve regeneration, cross-chest procedure

Journal: Restorative Neurology and Neuroscience, vol. 25, no. 2, pp. 131-141, 2007