High-resolution combinatorial 3D printing of gelatin-based biomimetic triple-layered conduits for nerve tissue engineering.

Peripheral nerve injury is a common clinical problem often requiring surgical nerve reconstruction. To this end, tissue-engineered conduit has been proved to be crucial for nerve reconstruction. Despite its progress in recent years, the design and fabrication of translational biomimetic nerve conduits is highly challenging. Therefore, this study aims to design and fabricate mechanically-tunable nerve conduits with biomimetic structural features of the human nerve suitable for nerve tissue engineering. Herein, we employed combinatorial approach comprising of electrohydrodynamic (EHD) jet printing, dip-coating, and electrospinning techniques for fabricating triple-layered conduits. The intricate structural details were achieved via high-resolution EHD jet printed PCL filaments with tunable directionality, as the innermost layer; followed by dip coating of gelatin hydrogels to form the middle layer, and lastly, wrapped with electrospun PCL nanofibers as an outer layer of the conduits. The mechanical properties, porosity, and biocompatibility of the fabricated conduits were studied and compared with control. The results of this study confirmed that the combinatorial approach has greater potential to fabricate mechanically-tunable triple-layered conduits with favorable neuronal precursor and vascular cell compatibility.