Pathogenesis of polypropylene mesh complications in female pelvic floor surgery.

Background: The pathogenesis of female pelvic floor polypropylene mesh complications is unclear as trials evaluating explanted mesh have not included asymptomatic controls.

Objectives: To compare explanted polypropylene mesh from those with and without mesh complications to determine the pathogenesis of the complications.

Methods: Between August 2019 and July 2020 66 participants attending Wesley and Royal Brisbane and Women's Hospital Urogynecology department with mesh complications and 15 undergoing repeat prolapse and/or continence surgery after prior polypropylene mesh implantation were included. Investigations included 14 histology and immunohistochemical biomarkers and a subgroup of 21 underwent scanning electron microscopy (SEM) to evaluate degradation and Fourier Transform Infrared Spectroscopy (FTIR) to determine if any degradation was secondary to oxidation from free radical oxygen species. All scoring was standardized and reviewers blinded to group allocation. Mean differences in biomarkers between cases and controls were estimated after accounting for intracluster correlation because of repeated measurements through generalized estimating equations using a linear model framework. Gwet's agreement coefficient assessed consistency in independent reviews, and Spearman's correlation explored biomarker relationships.

Results: Cases had significantly increased staining of smooth muscle antigen (SMA, suggesting myofibroblasts) (MD=0.65, p<0.01) and Masson Trichome (collagen)(MD=0.22, p=0.01) and lower levels of foreign body giant cells (FBGC) (MD=-0.39, p<0.01), blood vessels (MD=-0.34, p<0.01), CD86 (M1 macrophages) (p=0.05) and CD4 helper cells (MD=-0.58, p<0.01) as compared to control explants. Cases and controls demonstrated moderate and equal levels of degradation on histology, SEM (p=0.86) and oxidation on FTIR (p=0.01). Degradation correlated poorly with all biomarkers (r<0.04). Persistent and equal levels of CD206 (M2 macrophages), CD68 (total macrophages), CD45 (leucocytes), CD31 (endothelial cells) and CD8 (cytotoxic T Cell) were identified in cases and controls and the ratio of type I/III collagen was similar in both groups. Univariate analysis demonstrated prolapse mesh as compared to continence mesh was associated with increased FBGC's, CD86 marker, and histological degradation (p<=0.001). Post-menopausal status (p=0.04) was independently associated with increased degradation. Smoking was associated with increased type I collagen deposition (p=0.009) and lower FBGC's (p=0.03) as compared to non-smokers. Systemic hormone replacement therapy was associated with increased CD31 (p=0.01), FBGC (p=0.003), blood vessels (p=0.024), Sirius red staining for type three collagen (p=0.001) and decreased CD45 (p=0.009) when compared to non-users of systemic HRT. After duration and mesh type adjustment, FBGS, blood vessels, CD4, SMA, and Masson trichome remained significant between cases and controls. Multivariable analysis indicated histological degradation increased by a score of 0.1/year implantation (p<0.01) and was reduced in continence tapes as compared to prolapse mesh (MD -0.5 95% CI -0.8 to -0.2). Duration of implantation was also associated with increased Masson trichome score 0.02/year and SMA was increased in cases (MD 0.65 95% CI 0.3 to 1.0) and explanted prolapse meshes (MD 0.4 95% CI 0.02 to 0.7) as compared to continence tapes. Intra-observer scoring consistency on Gwets coefficient ranged from fair to very high.

Conclusion: While oxidation degradation was demonstrated in all polypropylene mesh explants we were unable to confirm this was the cause of complications that maybe related to increased fibrosis and myofibroblast activity possibly secondary to a prolonged inflammatory response.