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 8

Loss of CCR2 impairs fibroblast growth but does not hamper wound healing following mesh implantation.

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Loss of CCR2 impairs fibroblast growth but does not hamper wound healing...
(A) Sirius red staining of mesh explants isolated from WT and Ccr2–/– mice on day 21 after implantation. Inset images show magnified mesh-surrounding extracellular matrix. Scale bar: 400 μm; ×2 (inset). (B–D) In vitro fibroblast activation by mesh-explanted tissue. 5 × 104 NIH/3T3 fibroblasts were plated and grown for 12 hours initially. 0.5 cm2 explanted mesh derived from WT and Ccr2–/– mice isolated on day 21 after implantation was added to the cell cultures, and cells were allowed to grow for another 12 hours. Fibroblast activation was determined by in vitro time-lapse microscopy. (B) Phase-contrast images of fibroblast cell cultures. Cells were imaged continuously for a time period of 24 hours, showing control cells without addition of mesh explants (left) and cells in coculture with mesh tissue derived from Ccr2–/– mice (middle) and from WT control animals (right). (C and D) Statistical analysis of cell division detected by phase-contrast changes visualized in B. Cell division was calculated, determining the statistical mean of dividing cells visible in each time point (C) and also displayed over time (D) for control cells (blue), cells cultured with tissue from Ccr2–/– mice (green), and WT control mesh tissue (red). Error bars represent mean ± SD.