Tissue remodeling macrophages morphologically dominate at the interface of polypropylene surgical meshes in the human ab
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ORIGINAL ARTICLE
Tissue remodeling macrophages morphologically dominate at the interface of polypropylene surgical meshes in the human abdomen A. Dievernich1 · P. Achenbach2 · L. Davies3 · U. Klinge1 Received: 29 June 2020 / Accepted: 23 September 2020 © The Author(s) 2020
Abstract Background Mesh implants are widely used to reinforce the abdominal wall, although the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Macrophages are suspected to regulate the subsequent scar formation, but it is still unclear whether adequate fibrous scar formation with collagen deposition depends mainly on the presence of M1 or M2 macrophages. Methods This study investigated the FBR to seven human polypropylene meshes, which were removed after a median incorporation time of 1 year due to the primary complaint of recurrence. Using immunofluorescence, the FBR was examined in six regional zones with increasing distance from the mesh fibers up to 350 µm, based on the cell densities, macrophage M1 (CD86) and M2 (CD163, CD206) phenotypes, deposition of collagen-I and -III, and expression of matrix metalloproteinase-2 (MMP-2) and -8 as indicator of collagen degradation. Results All mesh–tissue complexes demonstrated a decrease in cell density and macrophages with distance to the mesh fibers. Overall, about 60% of the macrophages presented an M2 phenotype, whereas only 6% an M1 phenotype. Over 70% of macrophages showed co-expression with collagen-I or -III and over 50% with MMP-2. Conclusions The chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction. Keywords Foreign body reaction · Macrophage · Collagen · Mesh · Fluorescence microscopy
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10029-020-02315-2) contains supplementary material, which is available to authorized users. * A. Dievernich [email protected] 1
Department of General, Visceral and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany
2
Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany
3
Division of Infection and Immunity, Cardiff University, Cardiff, UK
Currently, textile mesh structures made of polypropylene are widely used to reinforce a hernia repair in the abdominal wall. The tissue reaction to the implants leads to the formation of a foreign body granuloma. Here, the mesh fibers are surrounded by dense layers of inflammatory cells with accompanying fibrotic encapsulation that shields the mesh from the surrounding tissue. After early recruitment of neutrophils, macrophages become the predominant cell mediator and are suspected to regulate
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