TY - JOUR
T1 - Polypropylene mesh implantation for hernia repair causes myeloid cell-driven persistent inflammation
AU - Heymann, Felix
AU - von Trotha, Klaus-Thilo
AU - Preisinger, Christian
AU - Lynen-Jansen, Petra
AU - Roeth, Anjali A.
AU - Geiger, Melanie
AU - Geisler, Lukas Jonathan
AU - Frank, Lanna Katharina
AU - Conze, Joachim
AU - Luedde, Tom
AU - Trautwein, Christian
AU - Binneboesel, Marcel
AU - Neumann, Ulf P.
AU - Tacke, Frank
N1 - Publisher Copyright:
© Copyright 2019, American Society for Clinical Investigation.
PY - 2019/1/24
Y1 - 2019/1/24
N2 - 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.
AB - 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.
KW - FOREIGN-BODY REACTION
KW - HOST TISSUE-RESPONSE
KW - MACROPHAGE PHENOTYPE
KW - LIVER FIBROSIS
KW - PORE-SIZE
KW - DIFFERENTIATION
KW - IMPACT
KW - HOMEOSTASIS
KW - INTERFACE
KW - MIGRATION
U2 - 10.1172/jci.insight.123862
DO - 10.1172/jci.insight.123862
M3 - Article
C2 - 30674727
SN - 2379-3708
VL - 4
JO - JCI INSIGHT
JF - JCI INSIGHT
IS - 2
M1 - 123862
ER -