Tissue Models for Neurogenesis and Repair in 3D

Development and maturation of vascular and neuronal tissues occurs simultaneously in utero, and are regulated by significant crosstalk. Here, the development of a 3D tissue system to model neurogenesis and recapitulate developmental signaling conditions is reported. Human umbilical vein endothelial cells (HUVECs) are seeded inside channels within collagen gels to represent nascent vascular networks. Axons extending from chicken dorsal root ganglia grow significantly longer and preferentially toward the HUVEC seeded channels with respect to unloaded channels. To replicate these findings without the vascular component, channels are loaded with brain-derived neurotrophic factor (BDNF), the principle signaling molecule in HUVEC-stimulated axonal growth, and axons likewise are significantly longer and grow preferentially toward the BDNF-loaded channels with respect to controls. This 3D tissue system is then used as an in vitro replicate for peripheral nerve injury, with neural repair observed within 2 weeks. These results demonstrate that the 3D tissue system can model neural network formation, can 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.