Development and maturation of vascular and neuronal tissues occurs simultaneously in utero, and are regulated by significant crosstalk. We report on the development of a 3D tissue system to model neurogenesis and recapitulate developmental signaling conditions. Human umbilical vein endothelial cells (HUVECs) were seeded inside channels within collagen gels to represent nascent vascular networks. Axons extending from chicken dorsal root ganglia (DRGs) grew significantly longer and preferentially towards the HUVEC seeded channels with respect to unloaded channels. To replicate these findings without the vascular component, channels were loaded with brain-derived neurotrophic factor (BDNF), the principle signaling molecule in HUVEC-stimulated axonal growth, and axons likewise were significantly longer and grew preferentially towards the BDNF-loaded channels with respect to controls. This 3D tissue system was then used as an in vitro replicate for peripheral nerve injury, with neural repair observed within 2 weeks. These results demonstrate that our 3D tissue system can model neural network formation, repair after laceration injuries, and can be utilized to further study how these networks form and interact with other tissues, such as skin or skeletal muscle.
Keywords: collagen; nerve repair; neurogenesis; neurovascular unit; tissue engineering.