Research
Gynecology
Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque

Presented at the Joint Scientific Meeting of the American Urogynecologic Society and International Urogynecologic Association, Washington, DC, July 22-26, 2014.
https://doi.org/10.1016/j.ajog.2015.08.002Get rights and content

Objective

We sought to determine the predominant cell type (macrophage, T lymphocyte, B lymphocyte, mast cell) within the area of implantation of the prototypical polypropylene mesh, Gynemesh PS (Ethicon, Somerville, NJ); and to determine the phenotypic profile (M1 proinflammatory, M2 antiinflammatory) of the macrophage response to 3 different polypropylene meshes: Gynemesh PS (Ethicon), and 2 lower-weight, higher-porosity meshes, UltraPro (Ethicon) and Restorelle (Coloplast, Humblebaek, Denmark).

Study Design

Sacrocolpopexy was performed following hysterectomy in rhesus macaques. Sham-operated animals served as controls. At 12 weeks postsurgery, the vagina-mesh complex was excised and the host inflammatory response was evaluated. Hematoxylin and eosin was used to perform routine histomorphologic evaluation. Identification of leukocyte (CD45+) subsets was performed by immunolabeling for CD68 (macrophage), CD3 (T lymphocyte), CD20 (B lymphocyte), and CD117 (mast cell). M1 and M2 macrophage subsets were identified using immunolabeling (CD86+ and CD206+, respectively), and further evaluation was performed using enzyme-linked immunosorbent assay for 2 M1 (tumor necrosis factor-alpha and interleukin [IL]-12) and 2 M2 (IL-4 and IL-10) cytokines.

Results

Histomorphologic evaluation showed a dense cellular response surrounding each mesh fiber. CD45+ leukocytes accounted for 21.4 ± 5.4% of total cells within the perimesh area captured in a ×20 field, with macrophages as the predominant leukocyte subset (10.5 ± 3.9% of total cells) followed by T lymphocytes (7.3 ± 1.7%), B lymphocytes (3.0 ± 1.2%), and mast cells (0.2 ± 0.2%). The response was observed to be more diffuse with increasing distance from the fiber surface. Few leukocytes of any type were observed in sham-operated animals. Immunolabeling revealed polarization of the macrophage response toward the M1 phenotype in all mesh groups. However, the ratio of M2:M1 macrophages was increased in the fiber area in UltraPro (P = .033) and Restorelle (P = .016) compared to Gynemesh PS. In addition, a shift toward increased expression of the antiinflammatory cytokine IL-10 was observed in Restorelle as compared to Gynemesh PS (P = .011).

Conclusion

The host response to mesh consists predominantly of activated, proinflammatory M1 macrophages at 12 weeks postsurgery. However, this response is attenuated with implantation of lighter-weight, higher-porosity mesh. While additional work is required to establish causal relationships, these results suggest a link among the host inflammatory response, mesh textile properties, and clinical outcomes in the repair of pelvic organ prolapse.

Section snippets

Meshes

The test articles consisted of 3 polypropylene meshes with varying textile and mechanical characteristics as previously described.12, 26 Briefly, specific weight and pore size were provided by the manufacturer. Porosity was determined using a custom-designed algorithm (Matlab, Version 8.0; Mathworks, Natick, MA) and stiffness was determined by ball burst testing. Table 1 shows the relevant mechanical and structural characteristics associated with each mesh. Of note, UltraPro is manufactured

Results

Animals had similar age, parity, and pelvic organ prolapse quantification (POP-Q) stage (Table 2). The POP-Q staging methods utilized were the same as that utilized in human beings adjusted to account for the shorter length of the macaque vagina.29 Animals in the Restorelle group weighed more than the other groups (P = .042); however, weight did not correlate with any of the measured outcomes (P > .36 for all). One animal in the study demonstrated a mesh exposure into the vagina. There were no

Comment

The present study sought to define the host inflammatory response to 3 polypropylene meshes with distinct textile properties following implantation via sacrocolpopexy in the rhesus macaque. The most significant findings were that, while all mesh materials elicited a predominantly M1 macrophage profile, lower-weight, higher-porosity meshes (UltraPro and Restorelle) elicited a shift in the M2/M1 macrophage ratio in the area around individual mesh fibers. The concentration of antiinflammatory

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This work was supported by National Institutes of Health awards R01 HD061811 (P.A.M.) and K12HD043441 (B.N.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding source had no involvement in the study design, collection of data, analysis of data, interpretation of data, writing of the report, or the decision to submit for publication.

The authors report no conflict of interest.

Cite this article as: Brown BN, Mani D, Nolfi AL, et al. Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque. Am J Obstet Gynecol 2015;213:668.e1-10.

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