Combining Electrospinning and Electrospraying to Prepare a Biomimetic Neural Scaffold with Synergistic Cues of Topography and Electrotransduction.

The nerve tissue consists of aligned fibrous nerve bundles, in which neurons communicate and transmit information through electrical signals. Hence, biocompatibility, oriented fibrous structure, and electrical conductivity are key factors for the biomimetic design of nerve scaffolds. Herein, we built a technical platform to combine electrospinning and electrospraying for preparing a biomimetic scaffold with conductivity and aligned fibrous structure. The highly aligned polycaprolactone (PCL) microfibrous scaffolds with co-sprayed collagen and conductive polypyrrole nanoparticles (PPy NPs) showed good bioactivity, supplying a platform for exploring the effects of topographical guidance, fiber conductivity, and its mediated external electrical signals on neurogenesis. The results revealed that collagen-coated highly aligned PCL microfibrous scaffold induced PC12 cells oriented and elongated along the direction of fibers. In addition, the improved conductivity of PPy-coated aligned fibers and its mediated external electrical stimulation collectively contributed to the functional expression, including elongation, gene expression, and protein expression, of PC12 cells. We further demonstrated the potential mechanism where the fiber conductivity and its mediated external electrical signals resulted in the upregulation of voltage-gated calcium channel, leading to the influx of Ca2+, thereby activating intracellular signaling cascades, ultimately enhancing neurogenesis. This approach provides a strategy to design aligned fibrillary scaffolds with bioactive adhesion domains and electroconductivity for neural regeneration.