Top

Hernia

Published in:

Open Access 01-12-2020 | Original Article

Tissue remodeling macrophages morphologically dominate at the interface of polypropylene surgical meshes in the human abdomen

Authors: A. Dievernich, P. Achenbach, L. Davies, U. Klinge

Published in: Hernia | Issue 6/2020

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.

Available only for authorised users

Anderson JM, Rodriguez A, Chang DT (2008) Foreign body reaction to biomaterials. Semin Immunol 20:86–100. https://doi.org/10.1016/j.smim.2007.11.004CrossRefPubMed

Stein M, Keshav S, Harris N, Gordon S (1992) Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 176:287–292. https://doi.org/10.1084/jem.176.1.287CrossRefPubMed

Mills CD, Kincaid K, Alt JM et al (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166–6173. https://doi.org/10.4049/jimmunol.164.12.6166CrossRefPubMed

Wang L, Zhang S, Wu H et al (2019) M2b macrophage polarization and its roles in diseases. J Leukoc Biol 106:345–358. https://doi.org/10.1002/JLB.3RU1018-378RRCrossRefPubMed

Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969. https://doi.org/10.1038/nri2448CrossRefPubMedPubMedCentral

Krzyszczyk P, Schloss R, Palmer A, Berthiaume F (2018) The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol. https://doi.org/10.3389/fphys.2018.00419CrossRefPubMedPubMedCentral

Brown BN, Mani D, Nolfi AL et al (2015) Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque. Am J Obstet Gynecol 213:668.e1–668.e10. https://doi.org/10.1016/j.ajog.2015.08.002CrossRef

Wolf MT, Dearth CL, Ranallo CA et al (2014) Macrophage polarization in response to ECM coated polypropylene mesh. Biomaterials 35:6838–6849. https://doi.org/10.1016/j.biomaterials.2014.04.115CrossRefPubMedPubMedCentral

Nolfi AL, Brown BN, Liang R et al (2016) Host response to synthetic mesh in women with mesh complications. Am J Obstet Gynecol 215:206.e1–206.e8. https://doi.org/10.1016/j.ajog.2016.04.008CrossRef

10.

Spiller KL, Koh TJ (2017) Macrophage-based therapeutic strategies in regenerative medicine. Adv Drug Deliv Rev 122:74–83. https://doi.org/10.1016/j.addr.2017.05.010CrossRefPubMedPubMedCentral

11.

Hachim D, LoPresti ST, Yates CC, Brown BN (2017) Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration. Biomaterials 112:95–107. https://doi.org/10.1016/j.biomaterials.2016.10.019CrossRefPubMed

12.

Hou J, Shi J, Chen L et al (2018) M2 macrophages promote myofibroblast differentiation of LR-MSCs and are associated with pulmonary fibrogenesis. Cell Commun Signal 16:89. https://doi.org/10.1186/s12964-018-0300-8CrossRefPubMedPubMedCentral

13.

Klinge U, Dievernich A, Tolba R et al (2020) CD68+ macrophages as crucial components of the foreign body reaction demonstrate an unconventional pattern of functional markers quantified by analysis with double fluorescence staining. J Biomed Mater Res JBM B. https://doi.org/10.1002/jbm.b.34639CrossRef

14.

Brown BN, Londono R, Tottey S et al (2012) Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater 8:978–987. https://doi.org/10.1016/j.actbio.2011.11.031CrossRefPubMed

15.

Pierce LM, Rao A, Baumann SS et al (2009) Long-term histologic response to synthetic and biologic graft materials implanted in the vagina and abdomen of a rabbit model. Am J Obstet Gynecol 200:546.e1–546.e8. https://doi.org/10.1016/j.ajog.2008.12.040CrossRef

16.

Pechkovsky DV, Prasse A, Kollert F et al (2010) Alternatively activated alveolar macrophages in pulmonary fibrosis—mediator production and intracellular signal transduction. Clin Immunol 137:89–101. https://doi.org/10.1016/j.clim.2010.06.017CrossRefPubMed

17.

Venosa A, Malaviya R, Choi H et al (2016) Characterization of distinct macrophage subpopulations during nitrogen mustard-induced lung injury and fibrosis. Am J Respir Cell Mol Biol 54:436–446. https://doi.org/10.1165/rcmb.2015-0120OCCrossRefPubMedPubMedCentral

18.

Wynn T, Barron L (2010) Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 30:245–257. https://doi.org/10.1055/s-0030-1255354CrossRefPubMedPubMedCentral

19.

Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737. https://doi.org/10.1038/nri3073CrossRefPubMedPubMedCentral

20.

Madsen DH, Leonard D, Masedunskas A et al (2013) M2-like macrophages are responsible for collagen degradation through a mannose receptor–mediated pathway. J Cell Biol 202:951–966. https://doi.org/10.1083/jcb.201301081CrossRefPubMedPubMedCentral

21.

Simões FC, Cahill TJ, Kenyon A et al (2020) Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair. Nat Commun 11:600. https://doi.org/10.1038/s41467-019-14263-2CrossRefPubMedPubMedCentral

22.

Schnoor M, Cullen P, Lorkowski J et al (2008) Production of type VI collagen by human macrophages: a new dimension in macrophage functional heterogeneity. J Immunol 180:5707–5719. https://doi.org/10.4049/jimmunol.180.8.5707CrossRefPubMed

23.

Jansen PL, Kever M, Rosch R et al (2007) Polymeric meshes induce zonal regulation of matrix metalloproteinase-2 gene expression by macrophages and fibroblasts. FASEB J 21:1047–1057. https://doi.org/10.1096/fj.06-6755comCrossRefPubMed

24.

Binnebösel M, von Trotha KT, Ricken C et al (2012) Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression. BMC Surg 12:1. https://doi.org/10.1186/1471-2482-12-1CrossRefPubMedPubMedCentral

25.

Vacek T, Rahman S, Yu S et al (2015) Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen sulfide, homocysteine, and polymorphisms. VHRM. https://doi.org/10.2147/VHRM.S68415CrossRef

26.

Davies LC, Taylor PR (2015) Tissue-resident macrophages: then and now. Immunology 144:541–548. https://doi.org/10.1111/imm.12451CrossRefPubMedPubMedCentral

27.

Rőszer T (2015) Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm 2015:1–16. https://doi.org/10.1155/2015/816460CrossRef

28.

Reinartz S, Schumann T, Finkernagel F et al (2014) Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse: macrophages in human ovarian carcinoma. Int J Cancer 134:32–42. https://doi.org/10.1002/ijc.28335CrossRefPubMed

29.

Brown BN, Valentin JE, Stewart-Akers AM et al (2009) Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials 30:1482–1491. https://doi.org/10.1016/j.biomaterials.2008.11.040CrossRefPubMedPubMedCentral

Title: Tissue remodeling macrophages morphologically dominate at the interface of polypropylene surgical meshes in the human abdomen
Authors: A. Dievernich
P. Achenbach
L. Davies
U. Klinge
Publication date: 01-12-2020
Publisher: Springer Paris
Published in: Hernia / Issue 6/2020
Print ISSN: 1265-4906
Electronic ISSN: 1248-9204
DOI: https://doi.org/10.1007/s10029-020-02315-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Tissue remodeling macrophages morphologically dominate at the interface of polypropylene surgical meshes in the human abdomen

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2020

Alterations in the mechanical, chemical and biocompatibility properties of low-cost polyethylene and polyester meshes after steam sterilization

Editor’s corner

Incisional hernia repair in a high-fidelity silicone model for open retro-muscular mesh implantation with preparation of the fatty triangle: validation and educational impact study

Long term comparative evaluation of two types of absorbable meshes in partial abdominal wall defects: an experimental study in rabbits

Comment on: Mesh erosion into the urinary bladder, rare condition but important to know

The emerging role of sarcopenia as a prognostic indicator in patients undergoing abdominal wall hernia repairs: a systematic review of the literature