The optimal conduit for nerve regeneration

Nerve regeneration has remained one of the major hurdles in reconstructive surgery. Despite continuous efforts to improve recovery, its complications and/or follow up surgeries severely impair the patients quality of life. Silk fibres possess favourable characteristics with regard to their flexibility, cell adhesion properties, and their superior biocompatibility and degradation properties compared to other materials. Over the recent years, native spider silk fibres showed to be an auspicious material as a filling material in artificial conduits for supporting nerve regeneration. Artificial nerve guidance conduits (NGCs), a tube inserted between the two injured nerve stumps, present a readily available alternative to the current gold standard, the nerve autograft. They offer a guidance structure for regenerating axons, while circumventing the disadvantages brought about by the harvest of autologous material. Yet, hollow NGCs have shown limitations as they fail to allow successful regeneration in supracritical nerve injuries, i.e. nerve defects larger than 3.0 cm. Our research group has extensive and unrivalled experience with spider silk fibres both in vitro and in vivo. We have demonstrated that spider silk fibres as a filling material in vein grafts promoted regeneration equal to the nerve autograft for a 6.0 cm nerve gap in sheep, thereby successfully repairing a nerve damage surpassing the critical length. Hence, the consecutive step, therefore, is to replace the vein grafts with artificial conduits and to elaborate this study using an off-the-shelf nerve conduit filled with spider silk fibres. Moreover, to exceed the 6.0 cm, we propose to combine multiple biomaterial luminal fillings. Besides fibres, hydrogels emerged as a possible filling material for artificial NGCs. While longitudinal fibres act as a guiding structure for regenerating axons, hydrogels provide a three-dimensional matrix that mimics the native tissue and adds structural integrity preventing long conduits from collapsing. We propose that spider silk fibres embedded in hydrogel have the potential of improving artificial NGCs to the point that the filled conduits become an equal alternative to the nerve autograft for long nerve defects. The extensive experience and expertise of our interdisciplinary team will provide the necessary knowhow which paves the path toward achieving these objectives. Univ.-Prof. Dr. med. Christine Radtkes long expertise in implementation of conduits for nerve regeneration will ensure reproducible experimentation, while her surgical background will support maintaining the path towards clinical applications. Lorenz Semmler is a PhD-student under the supervision of Prof. Radtke. While in medical school, he has performed his diploma thesis on spider silk filled conduits in rats in our lab, for which he applied several cutting-edge technologies. He has become a specialist in evaluating different functional outcome parameters in animal models. Flavia Millesi is a PhD student under the supervision of Prof. Radtke. She successfully analysed spider silk fibres of Nephila and their influence on cell adhesion, proliferation and migration in vitro. For this, she established multicolour immunofluorescence panels as well as migratory assays, which allowed detailed assessments of cell characteristics.