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Microtissue engineered neural networks as optically-controlled living electrodes for circuit modeling and neuroprosthetics / Oladayo Olaolu Adewole.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Adewole, Oladayo Olaolu, author.
- Language:
- English
- Subjects (All):
- Bioengineering.
- Biomedical engineering.
- Electrodes.
- Demutualization.
- Neurosciences.
- Bioengineering--Penn dissertations.
- Penn dissertations--Bioengineering.
- Local Subjects:
- Bioengineering.
- Biomedical engineering.
- Electrodes.
- Demutualization.
- Neurosciences.
- Bioengineering--Penn dissertations.
- Penn dissertations--Bioengineering.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (129 pages)
- Contained In:
- Dissertations Abstracts International 83-03B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2021.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Neural interfaces transmit signals between the nervous system and an external device throughthe activation of neuronal circuits (stimulation) or detection of neuronal activity (recording). Beyond research, these devices are used medically to restore or approximate neurologicalfunction, often following injury or disease-e.g., cochlear implants to provide auditory perception. However, current implantable neural interfaces use inorganic, rigid electrodes, inducing a foreignbodyresponse that limits their practical use for chronic medical applications. In this dissertation, we applied tissue engineering and optogenetic techniques to develop the first living, implantablemicrotissue engineered neural networks ("μTENNs") that can be controlled and monitored withlight as "living electrodes". These microtissues were fabricated with discrete, spheroidal cellpopulations ("aggregates") of multiple neuronal subtypes that projected long axons through anextracellular matrix (ECM) within a protective hydrogel cylinder ("microcolumn"). Fabrication andculture methodology were developed to optimize μTENN architecture and health. Longitudinalimaging, analysis, and immunocytochemistry of μTENNs were conducted to evaluate growth,viability, and network structure in vitro across multiple parameters including microtissue lengthand polarity. These studies also demonstrated that the aggregate fabrication method reproduciblygenerated μTENNs closely mimicking the connectome-i.e., locally connected circuits spannedby long axonal tracts. Calcium imaging and network analysis of single μTENNs and assemblies ofmulti-μTENN "chains" over time characterized their functional development and emergentnetwork-level properties across neuronal subtypes, with photostimulation demonstrating thatμTENN activity could be driven using optical input. Further, multi-μTENN studies established proof-of-concept for a modular approach to create and probe complex in vitro models of neuralcircuits. Finally, μTENNs expressing optical reporters were transplanted in rodent primary visualand auditory cortex and monitored through a transparent cranial window as early validation of theliving electrode strategy in vivo. Immunohistochemistry demonstrated that living electrodessurvived, projected neurites into host tissue, and maintained sufficient viability and structure toprovide optical output following transplant. In conclusion, this dissertation developed andcharacterized implantable living electrodes that may be built with a variety of cell types andcontrolled/monitored with light. These studies lay the foundation for optobiological modeling of theconnectome and neural interfacing with biologically-based devices.
- Notes:
- Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
- Advisors: Cullen, Daniel Kacy; Litt, Brian; Committee members: Meaney, David F.; Contreras, Diego.
- Department: Bioengineering.
- Ph.D. University of Pennsylvania 2021.
- Local Notes:
- School code: 0175
- ISBN:
- 9798535569437
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
- This item must not be sold to any third party vendors.
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