In vitro screening of inflammatory cell responses to polypropylene-based surgical mesh used in the treatment of pelvic organ prolapse
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Authors
Fennell, Kaylee
Date
2024-06-05
Type
thesis
Language
eng
Keyword
Biomaterials , Macrophages , Primary blood-derived mononuclear cells , Inflammation , Foreign Body Response
Alternative Title
Abstract
Up to 25% of women face complications from the transvaginal insertion of polypropylene-based mesh used to treat pelvic organ prolapse (POP) and stress urinary incontinence (SUI) as it was repurposed for gynecological surgery without pre-clinical or clinical testing. Foreign materials implanted in the body activate an immune response that can result in chronic inflammation often causing rejection of the material or pain. Explants from women with mesh complications have shown increased presence of inflammatory macrophages (M1) and fibrosis, which is likely influenced by the properties of the mesh (e.g., stiffness, pore size). In addition, hormonal modulation of the inflammatory response suggests that sexual dimorphism may exist in the immune response to foreign materials. This research aims to develop a novel in vitro method to screen inflammatory responses to surgical mesh to help investigate the mechanism causing the failure of mesh.
Polypropylene mesh used in the treatment of POP and SUI was characterized based on pore size and stiffness. Primary human peripheral blood-derived mononuclear cells (PBMCs) were isolated and used to evaluate monocyte and macrophage activation. A macrophage-like immortalized cell line (THP-1) was used in studies to evaluate the effect of female sex hormones (17β-estradiol and progesterone) and POP mesh on inflammatory responses of the macrophage phenotypes (unpolarized M0; pro-inflammatory M1; anti-inflammatory M2). The presence of inflammatory markers (IL-6 and TNF-α) for in vitro cell line studies were detected using qPCR and ELISA assays.
Characterization studies showed that SUI mesh is stiffer and has larger pore sizes compared to POP mesh. Although both are within the suggested ranges of design characteristics to help mitigate the foreign body response, they are made of different textile architectures that need to be further investigated to determine the clinical implication of these differences. Primary monocyte and macrophage studies showed that POP mesh elicits immune response activation via indicators of M1 macrophages (e.g., CD80, HLA-DR). Polarized THP-1 studies with POP mesh failed to show any significant changes in inflammatory gene expression (CD80, IL-6, TNF-α) or protein synthesis (IL-6, TNF-α). However, these lack in differences do not indicate a lack of response by cells, but rather could be attributed to mixed phenotype of cells in response to stimuli. Future work aims to determine sex-based differences between primary cell responses by obtaining more volunteers. This research contributes to the investigation of immune cell responses to surgical mesh, which will aid in the improvement of mesh materials and eventually allow for better clinical outcomes in the treatment of pelvic floor disorders.