Measuring the host response to deformed and tensioned polypropylene mesh

Objectives: Mesh deformations (pore collapse and wrinkling) with tensioning alter its structural properties resulting in varied material burden across the vagina. While the overall host response is that of stress shielding, areas of myofibroblast formation and fibrosis can occur in regions of high material burden and increased tissue stress such as that induced by tension. The macrophage response associated with mesh deformations is not known but likely directs downstream outcomes. We hypothesized that introduction of deformations into a mesh would be associated with an enhanced macrophage response, an increased density of smaller (more fragile) blood vessels, and increased collagen deposition – a response that would be increased in the presence of high tension.

Methods: Thirty-eight rhesus macaques underwent a total hysterectomy and complete transection of level I and II vaginal support (IACUC 16088646). A square-pored polypropylene mesh was implanted in 30 animals by sacrocolpopexy with 3 predefined geometries resulting in progressively increased material burden: stable (R0, square pore, open n=10), unstable (R45, diamond pore, collapsed n=10), and predeformed (RD, pores collapsed, mesh wrinkled, n=10) and placed at high tension (10N). Ten additional animals were implanted with RD on no tension (RDNT). Sham operated animals served as controls (N=8). At 12 weeks, mesh-vagina complexes were excised en bloc, embedded, sectioned at 7mm, and measured by analyzing the entire granulation tissue area minus the mesh area. Cellular and collagen density were quantified using H&E and Massons Trichrome. New blood vessel formation and size was measured via CD31. A pan-macrophage marker, CD68, was used to measure macrophages. A paired t-test was used for statistical analysis with the appropriate post-hoc testing.

Results: Animals had similar weight, gravidity, and parity. Pore collapse in the diamond configuration (R45) occurred mainly in the stem resulting in mesh elongation and decreased tension. Cellular density decreased with deformation (RD, p=0.037), and further decreased in the absence of tension (RDNT, p=0.0031) compared to R0, indicative of apoptosis and replacement of cells with granulation tissue (stress shielding). Collagen density decreased with decreased tension (R45, p=0.042), and further decreased with no tension (RDNT, p=0.0006). No significant differences were observed in vessel formation or vessel density. Macrophages surrounding fiber knots were increased with deformation (RD, p=0.012) and the absence of tension (RDNT, p=0.0006).

Conclusions: Together the decrease in collagen and increased proportion of macrophages in the absence of tension (RDNT) suggests that stress shielding prevails in this scenario due to the local stresses placed on the tissue by the mesh (ie mesh is stiffer than local vaginal ECM). Tension (RD) likely further increased tissue stresses activating myofibroblasts in response to these mechanical cues resulting in collagen deposition. Overall, the host response presents as net neutral collagen density balancing the opposing effects of shielding with fibrosis.