Comparative Analysis of Various Spider Silks in Regard to Nerve Regeneration: Material Properties and Schwann Cell Response.

Peripheral nerve reconstruction through the employment of nerve guidance conduits with Trichonephila dragline silk as a luminal filling has emerged as an outstanding preclinical alternative to avoid nerve autografts. Yet, it remains unknown whether the outcome is similar for silk fibers harvested from other spider species. This study compares the regenerative potential of dragline silk from two orb-weaving spiders, Trichonephila inaurata and Nuctenea umbratica, as well as the silk of the jumping spider Phidippus regius. Proliferation, migration, and transcriptomic state of Schwann cells seeded on these silks are investigated. In addition, fiber morphology, primary protein structure, and mechanical properties are studied. The results demonstrate that the increased velocity of Schwann cells on Phidippus regius fibers can be primarily attributed to the interplay between the silk's primary protein structure and its mechanical properties. Furthermore, the capacity of silk fibers to trigger cells toward a gene expression profile of a myelinating Schwann cell phenotype is shown. The findings for the first time allow an in-depth comparison of the specific cellular response to various native spider silks and a correlation with the fibers' material properties. This knowledge is essential to open up possibilities for targeted manufacturing of synthetic nervous tissue replacement.

Silk-in-Silk Nerve Guidance Conduits Enhance Regeneration in a Rat Sciatic Nerve Injury Model.

Advanced nerve guidance conduits can provide an off-the-shelf alternative to autografts for the rehabilitation of segmental peripheral nerve injuries. In this study, the excellent processing ability of silk fibroin and the outstanding cell adhesion quality of spider dragline silk are combined to generate a silk-in-silk conduit for nerve repair. Fibroin-based silk conduits (SC) are characterized, and Schwann cells are seeded on the conduits and spider silk. Rat sciatic nerve (10 mm) defects are treated with an autograft (A), an empty SC, or a SC filled with longitudinally aligned spider silk fibers (SSC) for 14 weeks. Functional recovery, axonal re-growth, and re-myelination are assessed. The material characterizations determine a porous nature of the conduit. Schwann cells accept the conduit and spider silk as growth substrate. The in vivo results show a significantly faster functional regeneration of the A and SSC group compared to the SC group. In line with the functional results, the histomorphometrical analysis determines a comparable axon density of the A and SSC groups, which is significantly higher than the SC group. These findings demonstrate that the here introduced silk-in-silk nerve conduit achieves a similar regenerative performance as autografts largely due to the favorable guiding properties of spider dragline silk.

Systematic Comparison of Commercial Hydrogels Revealed That a Synergy of Laminin and Strain-Stiffening Promotes Directed Migration of Neural Cells.

Hydrogels have shown potential in replacing damaged nerve tissue, but the ideal hydrogel is yet to be found. In this study, various commercially available hydrogels were compared. Schwann cells, fibroblasts, and dorsal root ganglia neurons were seeded on the hydrogels, and their morphology, viability, proliferation, and migration were examined. Additionally, detailed analyses of the gels' rheological properties and topography were conducted. Our results demonstrate vast differences on cell elongation and directed migration on the hydrogels. Laminin was identified as the driver behind cell elongation and in combination with a porous, fibrous, and strain-stiffening matrix structure responsible for oriented cell motility. This study improves our understanding of cell-matrix interactions and thereby facilitates tailored fabrication of hydrogels in the future.