Biomaterial and genetic tools to influence neuronal network formation, excitability, and maturity at the electrode interface
Understanding brain function remains a grand challenge of our time. Likewise, when neurodegeneration occurs, repair efforts are limited due to the highly heterogeneous and interconnected nature of the cerebral cortex. The drive to better understand normal brain function and pathological states has intensified demand for new technologies which can interrogate the nervous system with enhanced spatiotemporal resolution. Implanted brain electrodes are being used and developed to provide a deeper understanding for neurological injury and neurodegeneration. However, issues with biological integration come into play and potentially interfere with signal stability over time. Here, this work provides innovative tools that can be used to interface and control the tissue-electrode interface. In particular, we are interested in exploring surface chemistries, genetic tools, and electrode materials which favor neural regeneration around implanted electrodes. The research presented in this dissertation describes the exploration of biomaterial and genetic tools for interfacing the tissue-electrode interface: (1) characterization of surface chemistries presented to differentiating neural progenitors, and an understanding of the conditions which promote neurite outgrowth and electrophysiological maturation, (2) a blue-light inducible gene expression system, which could potentially be used to control gene expression at the implanted electrode interface, and (3) testing the impacts of "next-generation" electrode materials, such as diamond, as candidates for neural interfacing. Chapter 2 uncovers the study of various common substrates and their effects on rat neural progenitor cells, which can be used to create unique morphologies. Chapter 3 explores the use of an optogenetic system from a bacterial transcription factor (EL222) that allows for blue light-dependent transcriptional activation. Here, we validated the use of EL222 for spatial patterning of fluorescent reporter genes and developed stable expression in HEK293 cells, which can be used long-term for developing approaches for light-driven regeneration of neural circuitry. Chapter 4 reveals material and genetic factors that can affect cell structure and function. Here, we report the results of an initial characterization of the biocompatibility of the novel diamond-based materials, including conductive boron-doped polycrystalline diamond (BDD) and insulating polycrystalline diamond (PCD). The results presented will inform the transfer of the novel diamond substrate materials to sensing applications in the in vivo environment, where we expect to leverage the positive performance characteristics of the diamond materials displayed in vitro. Taken together, these chapters offer significant development of material and biological tools and that will help manage and mitigate challenges presented at the tissue-electrode interface. Future directions aim at exploring synergistic effects of electrode material and optogenetic control for controlling excitability and identity of cells at the interface, effectively bridging the divide between electronics and tissue.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- Attribution 4.0 International
- Material Type
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Theses
- Authors
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Setien-Grafals, Monica B.
- Thesis Advisors
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Purcell, Erin K.
- Committee Members
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Li, Wen
Qiu, Zhen
Arora, Ripla
- Date
- 2020
- Program of Study
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Biomedical Engineering - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- 134 pages
- ISBN
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9798698542612
- Permalink
- https://doi.org/doi:10.25335/bqh3-bw12