Preparation of tunable hollow composite microfibers assisted by microfluidic spinning and its application in the construction of in vitro neural models

Abstract

Microfluidic spinning, which has recently emerged as an important approach to processing hydrogels, can handle the flow in the fluid channel and generate microfibers in a controlled and mild manner, and therefore, it is suitable for cell loading, long-term culture, and tissue engineering. In this study, we utilized three-dimensional (3D) printing technology to prepare microfluidic chip templates with different microchannel heights in a one-step manner and obtained microfluidic spinning and microfiber assembly microchips. Hollow calcium alginate (CaA)/gelatin methacrylate (GelMA) composite microfibers were successfully prepared using a microfluidic spinning microchip combined with different fluid-injection strategies. The obtained hollow microfibers had one, two, or three lumens, and different inclusions could be added to the fiber walls. Hollow microfibers with a single lumen were used to load human umbilical vein endothelial cells (HUVECs) and exhibited good cell compatibility and barrier functions. We constructed a neural model based on the HUVEC-loaded hollow microfibers using a customized 3D printer. Using this established neural model, we induced the neural differentiation of rat adrenal medullary pheochromocytoma cells (PC12) using nerve growth factor. Axonal length, tubulin expression, and related gene (GAP-43 and TH) expression in PC12 cells were assessed. The current findings underscore the potential of utilizing microfluidic spinning in in vitro blood–brain barrier simulation, neuropharmaceutical and toxin evaluation, and brain-on-a-chip construction.