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- Title
- TISSUE ENGINEERED MYELINATION AND THE STRETCH REFLEX ARC SENSORY CIRCUIT: DEFINED MEDIUM FORMULATION, INTERFACE DESIGN AND MICROFABRICATION.
- Creator
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Rumsey, John, Hickman, James, University of Central Florida
- Abstract / Description
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The overall focus of this research project was to develop an in vitro tissue-engineered system that accurately reproduced the physiology of the sensory elements of the stretch reflex arc as well as engineer the myelination of neurons in the systems. In order to achieve this goal we hypothesized that myelinating culture systems, intrafusal muscle fibers and the sensory circuit of the stretch reflex arc could be bioengineered using serum-free medium formulations, growth substrate interface...
Show moreThe overall focus of this research project was to develop an in vitro tissue-engineered system that accurately reproduced the physiology of the sensory elements of the stretch reflex arc as well as engineer the myelination of neurons in the systems. In order to achieve this goal we hypothesized that myelinating culture systems, intrafusal muscle fibers and the sensory circuit of the stretch reflex arc could be bioengineered using serum-free medium formulations, growth substrate interface design and microfabrication technology. The monosynaptic stretch reflex arc is formed by a direct synapse between motoneurons and sensory neurons and is one of the fundamental circuits involved in motor control. The circuit serves as a proprioceptive feedback system, relaying information about muscle length and stretch to the central nervous system (CNS). It is composed of four elements, which are split into two circuits. The efferent or motor circuit is composed of an α-motoneuron and the extrafusal skeletal muscle fibers it innervates, while the afferent or sensory circuit is composed of a Ia sensory neuron and a muscle spindle. Structurally, the two muscular units are aligned in parallel, which plays a critical role modulating the system's performance. Functionally, the circuit acts to maintain appropriate muscle length during activities as diverse as eye movement, respiration, locomotion, fine motor control and posture maintenance. Myelination of the axons of the neuronal system is a vertebrate adaptation that enables rapid conduction of action potentials without a commensurate increase in axon diameter. In vitro neuronal systems that reproduce these effects would provide a unique modality to study factors influencing sensory neuronal deficits, neuropathic pain, myelination and diseases associated with myelination. In this dissertation, results for defined in vitro culture conditions resulting in myelination of motoneurons by Schwann cells, pattern controlled myelination of sensory neurons, intrafusal fiber formation, patterned assembly of the mechanosensory complex and integration of the complex on bio-MEMS cantilever devices. Using these systems the stretch sensitive sodium channel BNaC1 and the structural protein PICK1 localized at the sensory neuron terminals associated with the intrafusal fibers was identified as well as the Ca2+ waves associated with sensory neuron electrical activity upon intrafusal fiber stretch on MEMS cantilevers. The knowledge gained through these multi-disciplinary approaches could lead to insights for spasticity inducing diseases like Parkinson's, demyelinating diseases and spinal cord injury repair. These engineered systems also have application in high-throughput drug discovery. Furthermore, the use of biomechanical systems could lead to improved fine motor control for tissue-engineered prosthetic devices.
Show less - Date Issued
- 2009
- Identifier
- CFE0002904, ucf:48013
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002904
- Title
- THE PAST AND PENDING: USING CINEMA AS A DIALOGUE TO BREAK DOWN WALLS IN COMMUNICATION.
- Creator
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Torres, Samuel, Finch, Randy, University of Central Florida
- Abstract / Description
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The Past and Pending is a feature-length documentary by Samuel Eliot Torres, made as part of the requirements for earning a Master of Fine Arts in Film & Digital Media from the University of Central Florida. The film focuses on a family torn apart by a major decision to migrate to the U.S. from Puerto Rico. The protagonist, Torres, is now trying to receive closure from the events by asking the questions he could not ask as a child, but feels compelled to ask as an adult. Filming with only one...
Show moreThe Past and Pending is a feature-length documentary by Samuel Eliot Torres, made as part of the requirements for earning a Master of Fine Arts in Film & Digital Media from the University of Central Florida. The film focuses on a family torn apart by a major decision to migrate to the U.S. from Puerto Rico. The protagonist, Torres, is now trying to receive closure from the events by asking the questions he could not ask as a child, but feels compelled to ask as an adult. Filming with only one person in the crew allowed for an intimacy and spontaneity that is prized by entrepreneurial digital cinema makers. Without the financial and scheduling constraints of enlisting a large crew, the film was allowed to thrive with a spontaneous and ongoing shooting schedule, controlled entirely by one person.
Show less - Date Issued
- 2011
- Identifier
- CFE0003759, ucf:48789
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0003759
- Title
- TISSUE ENGINEERING THE MOTONEURON TO MUSCLE SEGMENT OF THE STRETCH REFLEX ARC CIRCUIT UTILIZING MICRO-FABRICATION, INTERFACE DESIGN AND DEFINED MEDIUM FORMULATION.
- Creator
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DAS, MAINAK, Hickman, James, University of Central Florida
- Abstract / Description
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The stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its...
Show moreThe stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its original length so as to prevent any kind of injury. It performs this compensation process using a simple negative feed back circuit called the stretch reflex arc. Any form of stretch in a muscle activates the stretch sensors (muscle spindle/ intrafusal fiber) lying deep in each muscle. After the stretch sensors get activated, it sends a train of signals to the spinal cord through the sensory neurons. The sensory neurons relay this information to the motoneuron. The motoneuron performs the necessary information processing and sends the message to the extrafusal fibers so as to compensate for the sudden stretch action. The motoneuron conveys this message to the extrafusal fibers by communicating through the special synaptic junctions called neuromuscular junctions. Based on this information, the extrafusal fibers act accordingly so as to counter the effect of sudden stretch. This is also called the monosynaptic stretch reflex that involves a single synapse between a sensory neuron and a motoneuron. To date studying these stretch reflex circuits is only feasible in animal models. Almost no effort has been made to tissue engineer such circuits for a better understanding of the complex development and repair processes of the stretch reflex circuit formation. The long-term goal of this research is to tissue engineer a cellular prototype of the entire stretch reflex circuit. The specific theme of this dissertation research was to tissue engineer the motoneuron to muscle segment of the stretch reflex arc circuit utilizing micro-fabrication, interface design and defined medium formulations. In order to address this central theme, the following hypothesis has been proposed. The first part of the hypothesis is that microfabrication technology, interface design and defined medium formulations can be effectively combined to tissue engineer the motoneuron to muscle segment of the stretch reflex arc. The second part of the hypothesis is that different growth factors, hormones, nanoparticles, neurotransmitters and synthetic substrate can be optimally utilized to regenerate the adult mammalian spinal cord neurons so as to replace the embryonic motoneurons in the stretch reflex tissue engineered construct with adult motoneurons. In this body of work, the different tissue engineering strategies and technologies have been addressed to enable the recreation of a in vitro cellular prototype of the stretch reflex circuit with special emphasis on building the motoneuron to muscle segment of the circuit. In order to recreate the motoneuron to muscle segment of the stretch reflex arc, a successful methodology to tissue engineer skeletal muscle and motoneuron was essential. Hence the recreation of the motoneuron to muscle segment of the stretch reflex circuit was achieved in two parts. In the part 1 (Chapters 2-5), the challenges in skeletal muscle tissue engineering were examined. In part 2 (Chapters 6-7), apart from tissue engineering the motoneuron to muscle segment, the real time synaptic activity between motoneuron and muscle segment were studied using extensive video recordings. In part 3 (Chapters 8-10), an innovative attempt had been made to tissue engineer the adult mammalian spinal cord neurons so that in future this technology could utilized to replace the embryonic neurons used in the stretch reflex circuit with adult neurons. The advantage of using adult neurons is that it provides a powerful tool to study older neurons since these neurons are more prone to age related changes, neurodegenerative disorders and injuries. This study has successfully demonstrated the recreation of the motoneuron to muscle segment of the stretch reflex arc and further demonstrated the successful tissue engineering strategies to grow adult mammalian spinal cord neurons. The different cell culture technologies developed in these studies could be used as powerful tools in nerve-muscle tissue engineering, neuro-prosthetic devices and in regenerative medicine.
Show less - Date Issued
- 2008
- Identifier
- CFE0002501, ucf:47679
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002501
