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Evaluating the Inflammatory and Tissue Remodeling Response to Novel Biomaterials in a Rabbit Model of Lumbar Colpopexy

Iftikhar, Aimon (2020) Evaluating the Inflammatory and Tissue Remodeling Response to Novel Biomaterials in a Rabbit Model of Lumbar Colpopexy. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Pelvic floor disorders account for the weakened function of muscles and surrounding tissues with one of the most prevalent conditions being pelvic organ prolapse (POP). Over a million women each year in the United States are affected with over a quarter undergoing a reconstructive procedure, increasingly using polypropylene mesh. While mesh may provide the mechanical support necessary to treat POP, serious complications such as exposure, erosion, contraction, and pain limit successful outcomes in the long term. Researchers have found an increased inflammatory response to mesh to be correlated with mesh complications, both pre-clinically and in the clinic. The host-biomaterial interaction, with a specific focus on early macrophage behavior, has been accepted as an indicator of implant integration in the long term. However, to date, most research on the host response to mesh has not been performed using a relevant animal model, or has only been evaluated in the long term.
The present dissertation focuses on understanding the tissue specific micro-environment of pelvic floor repair by employing the New Zealand white rabbit to perform a “gold standard” lumbar colpopexy procedure to evaluate changes in the immunologic response at acute (14 days) stages and tissue remodeling outcomes at late stages (90 days) of mesh implantation. Additional comparisons were made with subcutaneous implantation sites relevant from previous models studying host response. Histological and gene expression analysis found evidence of acute and chronic inflammation surrounding mesh implants with tissue degradation and unresolved inflammation. An overall heightened host response in vaginally implanted meshes was observed when considering macrophage presence, collagen deposition, elastic fiber changes and vascularity.
Further work to mitigate the observed tissue degradation and inflammation involved the immunomodulatory strategy of delivering interleukin-4 (IL-4) during the early stages of the host response. Studies in a mice subcutaneous implantation model have shown success in reducing fibrous capsule formation and encouraging a pro-remodeling response. We have taken this a step further in a novel clinically relevant New Zealand white rabbit lumbar colpopexy model. Results showed overall increased anti-inflammatory cytokine expression, with decreased tissue degradation, enhanced tissue integration, and an overall reduction in tissue adhesions.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Iftikhar, Aimonaii6@pitt.eduaii6
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBrown, Bryanbnb9@pitt.edubnb9
Date: 3 August 2020
Date Type: Publication
Defense Date: 3 February 2020
Approval Date: 3 August 2020
Submission Date: 1 April 2020
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 196
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: Host Response, Rabbit Lumbar Colpopexy, Regenerative Medicine, Cytokine Release
Date Deposited: 03 Aug 2021 05:00
Last Modified: 03 Aug 2021 05:15

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