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Bioengineered Urethral Augmentation

Haworth, Donna J. (2010) Bioengineered Urethral Augmentation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Urethral dysfunction is a common complication of many conditions including diabetes mellitus, spinal cord injury, vaginal childbirth, and pelvic trauma. Stress urinary incontinence (SUI) is the involuntary loss of urine due to the inability of the urethral sphincter to maintain a tight seal during the storage phase and is a condition that physically and emotionally affects millions of women. Currently treatments for SUI show limited effectiveness and/or complications. Regenerative medicine techniques may improve function and support of the diseased urethra. We hypothesized that exposure of bone marrow progenitor cells to mechanical stimuli would differentiate these cells to a contractile smooth muscle cell phenotype. This hypothesis was tested with the use of a bioreactor to aid in the differentiation via mechanical and/or chemical stimulation. In addition, an animal model of SUI was used to assess how the structural, functional and mechanical properties of the urethra were affected by placement of the tissue engineered urethral wrap (TEUW) around the native urethra.Our results indicate that bioreactor culture caused an up-regulation of myosin heavy chain, a contractile smooth muscle cell marker, with the highest expression seen after 10 days of culture with transforming growth factor beta. While some differentiation was observed, bioreactor conditions were not sufficient to create a fully functional TEUW. Exploration of stimulation regimens similar to what is seen by the urethra may cause further differentiation of these cells towards a smooth muscle phenotype. No differences between in-vivo groups were observed in leak point pressure results, but mechanical and pharmacological assessments indicated that the TEUW provided support to the urethra with responses more similar to controls than to SUI animals. Although ex-vivo results are promising, placement of the TEUW as a full wrap required separation of the urethra from the vagina, which appeared to cause remodeling and possibly scar formation. This separation may have contributed to the discrepancies seen between our in-vivo and ex-vivo data. Continued exploration of the benefits of the TEUW could include an animal model which receives the TEUW as only a partial wrap, attached to only the dorsal urethra, negating the need for tissue separation.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Haworth, Donna
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairVorp, David
Committee MemberMarra, Kaceymarrak@upmc.eduKGM5
Committee MemberYoshimura, Naokiyoshimuran@upmc.eduNYOS
Committee MemberRoy, Parthaproy@engr.pitt.eduPAR19
Committee MemberDegroat, William Cwcd2@pitt.eduWCD2
Date: 26 January 2010
Date Type: Completion
Defense Date: 17 September 2009
Approval Date: 26 January 2010
Submission Date: 29 September 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
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: biomechanics; tissue engineering; urethra
Other ID:, etd-09292009-135646
Date Deposited: 10 Nov 2011 20:02
Last Modified: 19 Dec 2016 14:37


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