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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)

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.

Original languageEnglish
Article number123862
Number of pages20
JournalJCI INSIGHT
Volume4
Issue number2
DOIs
Publication statusPublished - 24 Jan 2019

Keywords

  • FOREIGN-BODY REACTION
  • HOST TISSUE-RESPONSE
  • MACROPHAGE PHENOTYPE
  • LIVER FIBROSIS
  • PORE-SIZE
  • DIFFERENTIATION
  • IMPACT
  • HOMEOSTASIS
  • INTERFACE
  • MIGRATION

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