Immune response may drive pelvic floor polypropylene mesh complications

In a comparative analysis of explanted pelvic floor polypropylene (PP) meshes published in the American Journal of Obstetrics & Gynecology, researchers found that immune-mediated fibrosis and vascular changes, rather than oxidative degradation, were associated with symptomatic mesh complications.¹

PP mesh has been linked to increased pain in both female stress urinary incontinence and vaginal prolapse.² Therefore, the study aimed to investigate the underlying pathogenesis of PP mesh complications by determining whether mechanical or oxidative degradation of the material, or the host immune response, primarily drives adverse clinical outcomes.¹

"Although some investigators have found that low-volume surgeons have an increased rate of mesh complications compared with higher-volume surgeons, the data are generally conflicting, and this hypothesis will not be the subject of this manuscript," noted investigators.

PP mesh assessment

This comparative cross-sectional study was conducted between August 2019 and July 2020 at the Royal Brisbane and Women’s Hospital and the Wesley Urogynaecology Unit. Women who underwent PP mesh removal for pelvic pain or recurrent vaginal mesh exposure were included as cases. Asymptomatic controls were women with prior pelvic floor PP mesh placement who consented to opportunistic removal during elective prolapse or continence surgery.

Eligibility required an explant of at least 5 cm to permit adequate sampling for histology, microbiology, immunohistochemistry, scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. Women who declined participation were excluded.

Demographic and clinical variables collected included patient age at implantation and explantation, mesh type, duration of implant, parity, menopausal status, hormone therapy use, smoking status, diabetes mellitus, and prior hysterectomy. Mesh specimens were transported in 4% paraformaldehyde for up to 24 hours, washed, and stored in 70% ethanol before analysis.

Histologic and immunochemical evaluation

All specimens underwent standardized staining and assessment by 3 gynecologic pathologists blinded to group allocation. Hematoxylin and eosin, Masson trichrome, and Sirius red stains were used to evaluate fibrosis, vascularity, and collagen composition.

Immunohistochemistry targeted inflammatory and vascular markers, including CD4 (T-helper cells), CD8 (cytotoxic T cells), CD45 (leukocytes), CD68 (macrophages), CD86 (M1 macrophages), CD206 (M2 macrophages), CD31 (endothelial cells), and α–smooth muscle actin (α-SMA; myofibroblasts).

Histologic degradation was scored from 0 to 3, with higher scores indicating greater surface deterioration of mesh fibers. Sirius red staining differentiated type 1 (red/yellow) and type 3 (green) collagen under polarized light. SEM was used to assess microstructural cracking, and FTIR spectroscopy was applied to detect oxidation via specific spectral peaks.

Mesh results

A total of 81 PP mesh explants were analyzed from 74 women (66 cases and 15 controls). Among all explants, 63% were continence tapes and 37% were prolapse meshes. The mean implant duration was 8 years. No significant group differences were observed for age, body mass index, parity, or duration of implantation.

On histologic analysis, explants from symptomatic cases exhibited increased α-SMA staining (β = 0.65; 95% CI, 0.28–1.01; P < .001) and Masson trichrome fibrosis scores (β = 0.22; 95% CI, 0.05–0.39; P = .012) compared with controls. These findings indicated heightened myofibroblast activity and collagen deposition.

Conversely, cases had significantly fewer foreign body giant cells (β = −0.39; P = .001), reduced blood vessel counts (β = −0.34; P = .004), and lower CD4 (β = −0.58; P = .005) and CD86 (β = −0.31; P = .051) expression than controls.

No significant difference in histologic degradation was identified between groups (mean, 2.13 vs 2.12; P = .98). SEM findings confirmed moderate degradation across all samples (mean score, 2.7) with no variation by symptom status (P = .86).

Degradation observations

FTIR spectroscopy demonstrated oxidation in all explants, but oxidative degradation was comparable between cases and controls (P = .09). Degradation correlated poorly with inflammatory and fibrotic markers (r < 0.4).

Subgroup analyses revealed associations between postmenopausal status and increased degradation, and between systemic hormone replacement therapy and greater vascular density and collagen type III presence. Diabetes mellitus correlated with reduced vascularity, while smoking was linked to increased type 1 collagen.

Among symptomatic cases, meshes removed for pain exhibited lower α-SMA and CD31 levels than those removed for exposure, suggesting differential myofibroblast and angiogenic responses between clinical phenotypes.

Summary of findings

Across both symptomatic and asymptomatic groups, PP mesh demonstrated similar oxidative and structural degradation. However, the tissue surrounding symptomatic meshes displayed increased fibrosis, reduced vascularity, and enhanced myofibroblast activity, consistent with a persistent inflammatory state.

According to investigators, these findings support a pathophysiologic model in which host immune and fibrotic responses, rather than material oxidation alone, contribute to mesh-related pelvic floor complications.

"Although these findings do not support a direct correlation between PP mesh degradation and pelvic floor complications, it is important to recognize that a nonsignificant relationship with higher rates of oxidation in cases than in controls was identified and may prove significant with larger sample size evaluation," wrote investigators.

References

1. Maher C, Yeung E, Chen Z, et al. Pathogenesis of polypropylene mesh complications in female pelvic floor surgery. Am J Obstet Gynecol. 2025;233:309.e1-11. doi:10.1016/j.ajog.2025.03.009
2. Hiltunen R, Nieminen K, Takala T, et al. Low-weight polypropylene mesh for anterior vaginal wall prolapse: a randomized controlled trial. Obstet Gynecol. 2007;110(2 Pt 2):455-62. doi:10.1097/01.AOG.0000261899.87638.0a