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

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 4

Intravital 2-photon laser-scanning microscopy imaging of abdominal meshes following adoptive Actin-DsRed+ BM cell transfer.

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Intravital 2-photon laser-scanning microscopy imaging of abdominal meshe...
2 × 107 BM cells from Actin-DsRed donor mice were transferred i.v. into mesh-implanted mice and followed by intravital 2-photon laser-scanning microscopy (TPLSM) imaging (imaging for up to 3 hours). (A) Representative images of the experimental setting and schematic overview of the experimental design. (B) TPLSM images of cellular infiltrates at early stages of foreign body reaction (top row). Cells were injected 12 hours following surgery and analyzed at day 1, day 4, and day 7 (acute FBR). Imaging at day 21 (bottom row) was commenced following cell injection 1, 14, and 20 days before imaging (chronic FBR). Images were composed of 4 adjacent view fields. Mesh fibers are visible as either black or highly fluorescent coherent structures. Blue fibers show collagen fibers visualized by second harmonic generation. Scale bar: 200 μm. Statistical analysis was performed by cell counting in at least 4 view fields of surrounding mesh fibers with a penetration depth of 200 μm. (C) Flow cytometric assessment of cellular infiltration visible in B. Cells were stained for CD45, Ly6G, CD11b, F4/80, CD11c, I-Ab, Ly6C, and CD16. Cells were gated as CD45+Ly6G–DsRed+ cells and for quantification of relative monocyte recruitment efficacy. (D) Flow cytometric subtyping of cellular infiltrates from DsRed+ cells after 14 days (day 7→day 21). Cells were pregated as CD45+Ly6G–DsRed+ and analyzed for their expression of the indicated surface markers. Expression strength was quantified by calculating the MFI of the indicated markers. Exemplary results are shown in the dot plots; statistical analysis was performed from ≥3 animals per group. Student’s t test: *P < 0.05; **P < 0.01. Error bars represent mean ± SD.