Patterned and Functionalized Nanofiber Scaffolds in 3-Dimensional Hydrogel Constructs Enhance Neurite Outgrowth and Directional Control [Research Article in PubMed]
Brief Summary: Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. Biocompatible and biodegradable nanofibers were patterned and embedded within cellularized hydrogel constructs. Constructs with aligned nanofibers were shown to enable significant control over the direction of neurite outgrowth in both 2-dimensional (2D) and 3-dimensional (3D) neuronal cultures. Nanofibers that were functionalized with certain cell attachment molecules and then embedded in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. This work showed the ability to design and create unique 3-dimensional neural tissue constructs using a combined system of hydrogel and nanofiber scaffolding. These patterned and biofunctionalized 3D nanofiber scaffolds can control direction and increase length of neurite outgrowth in 3-dimensions and therefore hold much potential for neural tissue engineering.
Altogether this work demonstrates a novel approach for creating 3D patterned scaffolds for guiding neurite outgrowth of neuronal cultures, and this approach offers advancements in the development of implantable neural tissue constructs that enable control of neural development and reproduction of neuroanatomical pathways down to the subcellular level, with the ultimate goal of achieving functional neural regeneration. This study serves as a proof-of-concept that 3D neural tissue architecture can be assembled with seeding of induced stem cells on functionalized scaffolding. Future work will attempt more complex patterning to replicate neuroanatomical structures of the spinal cord, cortex, hippocampus, and other structures, as well as seeding with induced pluripotent stem cells, thereby opening the possibility of treating neurological tissue damage with a patient’s own cells on scaffolding that replicates innate neural architecture. These scaffolds would be directly applicable to specific areas of damage that are amenable to graft implantation, particularly spinal cord injuries, nerve injuries, tumor resection sites, and areas of stroke and cortical damage. This work may also play an important role as a novel therapeutic approach to many diseases of neural tissue, including traumatic brain injury and neurodegenerative diseases, and it will enable the creation of 3D in vitro models of neural damage and disease by replicating the innate cellular environment of human neurons made from induced stem cells of patients, thereby overcoming many problems with animal models that often fail to replicate the full array of features seen in humans.
McMurtrey RJ. Patterned and Functionalized Nanofiber Scaffolds in 3-Dimensional Hydrogel Constructs Enhance Neurite Outgrowth and Directional Control. J. Neural Eng. 11 (2014) 066009 doi:10.1088/1741-2560/11/6/066009 PMID: 25358624 arXiv:1501.01338
McMurtrey RJ. Novel Advancements in Three-Dimensional Neural Tissue Engineering and Regenerative Medicine. Neural Regeneration Research. 2015 Mar; 10(3):352-354. doi: 10.4103/1673-5374.153674 PMID: 25878573 arXiv:1504.00698
McMurtrey RJ. Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids. Tissue Engineering Part C. doi: 10.1089/ten.TEC.2015.0375 PMID: 26650970 arXiv:1512.06475
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