Holistic Analysis of Material Properties in Phylogenetically Diverse Spider Silks and Their Influence on Cell Adhesion

Abstract Reconstruction of long‐segment peripheral nerve gaps remains a clinical challenge, as neither autografts nor FDA‐approved nerve conduits achieve satisfactory functional recovery. Conduits filled with native Trichonephila dragline silk show promise for nerve defects exceeding the critical length, but translating natural silk to clinical use has limitations, necessitating research into recombinant silk replica. The search for optimal silk templates is ongoing, with numerous spider species still unexplored. This study aims to compare the ability of four native silk fibers from phylogenetically diverse spider families to support nerve regeneration. The influence of fiber morphology, primary and secondary protein structures, surface charge, chemical composition, and mechanical properties on the initial cell attachment is studied. Results demonstrate that silk collected from Peucetia lucasi do not adequately support Schwann cell adhesion, which is caused by the lack of a lipid layer and the limited fiber wettability. This reduced wettability, governed by the ratio of hydrophilic and hydrophobic amino acids of silk, is particularly relevant when considering the deployment of uncoated artificial silk fibers for neural tissue engineering. This knowledge is crucial for paving the way toward full functional recovery after peripheral nerve injury via implanting advanced synthetic nerve guidance conduits enhanced with luminal silk alternatives.