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Polypropylene mesh implantation for hernia repair causes myeloid cell–driven persistent inflammation
Felix Heymann, … , Ulf P. Neumann, Frank Tacke
Felix Heymann, … , Ulf P. Neumann, Frank Tacke
Published January 24, 2019
Citation Information: JCI Insight. 2019;4(2):e123862. https://doi.org/10.1172/jci.insight.123862.
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Research Article Gastroenterology Inflammation

Polypropylene mesh implantation for hernia repair causes myeloid cell–driven persistent inflammation

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Abstract

Polypropylene meshes that are commonly used for inguinal hernia repair may trigger granulomatous foreign body reactions. Here, we show that asymptomatic patients display mesh-associated inflammatory granulomas long after surgery, which are dominated by monocyte-derived macrophages expressing high levels of inflammatory activation markers. In mice, mesh implantation by the onlay technique induced rapid and strong myeloid cell accumulation, without substantial attenuation for up to 90 days. Myeloid cells segregated into distinct macrophage subsets with separate spatial distribution, activation profiles, and functional properties, showing a stable inflammatory phenotype in the tissue surrounding the biomaterial and a mixed, wound-healing phenotype in the surrounding stromal tissue. Protein mass spectrometry confirmed the inflammatory nature of the foreign body reaction, as characterized by cytokines, complement activation, and matrix-modulating factors. Moreover, immunoglobulin deposition increased over time around the implant, arguing for humoral immune responses in association with the cell-driven inflammation. Intravital multiphoton microscopy revealed a high motility and continuous recruitment of myeloid cells, which is partly dependent on the chemokine receptor CCR2. CCR2-dependent macrophages are particular drivers of fibroblast proliferation. Thus, our work functionally characterizes myeloid cell–dependent inflammation following mesh implantation, thereby providing insights into the dynamics and mechanisms of foreign body reactions to implanted biomaterials.

Authors

Felix Heymann, Klaus-Thilo von Trotha, Christian Preisinger, Petra Lynen-Jansen, Anjali A. Roeth, Melanie Geiger, Lukas Jonathan Geisler, Anna Katharina Frank, Joachim Conze, Tom Luedde, Christian Trautwein, Marcel Binnebösel, Ulf P. Neumann, Frank Tacke

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Figure 1

Characterization of cellular infiltrates in human and murine mesh samples.

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Characterization of cellular infiltrates in human and murine mesh sample...
(A) Histological analysis of foreign body granulomatous reaction from a patient explanted >1 year following mesh implantation (H&E). Cells were further subtyped using immunohistochemistry with the indicated antibodies. CD68 was costained with CD45 to estimate the proportion of mesh-infiltrating macrophages. Scale bar: 100 μm. (B) Flow cytometric analysis of myeloid subpopulations and their activation isolated from human mesh explants. Exemplary results are shown. n ≥ 3 samples were analyzed for flow cytometry and histology. (C) Mean fluorescence intensity (MFI) for macrophage markers expressed on the populations described in B. (D–H) Foreign body–induced inflammation was assessed in mice subjected to mesh implantation after 7, 21, and 90 days. Histological analysis of mesh-implanted (D) and sham-operated (E) animals. Scale bar: 100 μm. Cellular infiltration was analyzed by H&E histology and immunohistochemistry. (F) Quantification of total leukocyte infiltrates by flow cytometry 7 and 21 days following implantation. (G) Exemplary gating to characterize myeloid cell populations in the foreign body reaction. (H) Relative and absolute quantification of leukocyte subpopulations of the populations shown in G. MoMF, monocyte-derived macrophages. Statistical analysis was performed with at least 4 animals per group in 2 independent sets of experiments; experimental data were pooled for statistical analysis. Student’s t test: *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001. Error bars represent mean ± SD.

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