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Soft silicone-based neural interface to improve bladder function

Kumar, Ritesh (2023) Soft silicone-based neural interface to improve bladder function. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Lower urinary tract dysfunction is a serious ongoing medical complication that persists after spinal cord injury, multiple sclerosis, and diabetes mellitus. Losing the ability to empty the bladder voluntarily can significantly impact quality of life, and the current standard to treat this loss of control – intermittent catheterization – is associated with a high risk of urinary tract infections. Many neuromodulation interventions have been explored to empty the bladder but have not been translated to the clinic. Here, we designed a neural interface to electrically stimulate the bladder itself to evoke bladder emptying. Despite prior attempts in animals and people over the past decades, the success of direct bladder wall stimulation (DBWS) was limited by mechanical incompatibilities between the rigid electrodes and bladder tissue, especially during large volume changes, as well as by stimulation-induced co-activation of the urethra, legs, and other pelvic organs.
First, we designed a stretchable silicone electrode net that can be placed around the bladder, mapped the sensitivity of the bladder surface, and determined that the bladder base was the most sensitive location to stimulate in cats. We also minimized stimulation-induced co-activation of nearby muscles using different stimulation paradigms. Second, we created implantable versions of these electrode nets and tested them chronically in cats with and without anesthesia for 2-3 months. Direct bladder wall stimulation through various electrode configurations, temporal patterns, and stimulus intensities generated complete bladder emptying up to 15 weeks. In behaving cats, DBWS at different stimulus intensities elicited different voiding behaviors and could generate efficient voiding at physiological bladder pressures. Third, we studied the neural mechanisms through which DBWS operates and found that robust contractions could be generated with or without peripheral innervation of the bladder, likely by activating post-ganglionic fibers in the bladder itself, but that activation of sensory pathways in the intact nervous system led to larger contractions at lower stimulus amplitudes.
Overall, experiments in cats demonstrated that these electrodes could be an effective neural interface to generate comfortable, complete bladder emptying and could be used after injury or disease where the bladder is underactive or atonic.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kumar, Riteshrik18@pitt.edurik180000-0003-3614-1350
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGaunt, Robert Arag53@pitt.edurag53
Committee MemberFisher, Lee Elef44@pitt.edulef44
Committee MemberCui, Xinyanxic11@pitt.eduxic11
Committee MemberBoninger, Michael L.boninger@upmc.eduboninger
Date: 13 June 2023
Date Type: Publication
Defense Date: 30 August 2022
Approval Date: 13 June 2023
Submission Date: 21 February 2023
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 148
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: neuroprostheses, electrical stimulation, bladder control
Date Deposited: 13 Jun 2023 14:06
Last Modified: 13 Jun 2023 14:06
URI: http://d-scholarship.pitt.edu/id/eprint/44224

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