ObjectiveTo explore the preparation method, physical and chemical properties, and biocompatibility of a conductive composite scaffold based on polypyrrole/silk fibroin (PPy/SF) fiber with " shell-core” structure, and to provide a preliminary research basis for the application in the field of tissue engineered neuroscience.Methods The conductive fibers with " shell-core” structure were prepared by three-dimensional printing combined with in-situ polymerization. PPy/SF fiber-based conductive composite scaffolds were formed by electrospinning. In addition, core-free PPy conductive fibers and SF electrospinning fibers were prepared. The stability, biomechanics, electrical conductivity, degradation performance, and biological activity of each material were tested to analyze the comprehensive properties of fiber-based conductive composite scaffolds.ResultsCompared with pure core-free PPy conductive fibers and SF electrospinning fibers, the PPy/SF fiber-based conductive composite scaffolds with " shell-core” structure could better maintain the stability performance, enhance the mechanical stretchability of the composite scaffolds, maintain long-term electrical activity, and improve the anti-degradation performance. At the same time, PPy/SF conductive composite scaffolds were suitable for NIH3T3 cells attachment, conducive to cell proliferation, and had good biological activity.ConclusionPPy/SF fiber-based conductive composite scaffolds meet the needs of conductivity, stability, and biological activity of artificial nerve grafts, and provide a new idea for the development of a new generation of high-performance and multi-functional composite materials.