Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials - PubMed (original) (raw)

Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials

Bryan N Brown et al. Acta Biomater. 2012 Mar.

Erratum in

Abstract

Macrophages have been classified as having plastic phenotypes which exist along a spectrum between M1 (classically activated; pro-inflammatory) and M2 (alternatively activated; regulatory, homeostatic). To date, the effects of polarization towards an M1 or M2 phenotype have been studied largely in the context of response to pathogen or cancer. Recently, M1 and M2 macrophages have been shown to play distinct roles in tissue remodeling following injury. In the present study, the M1/M2 paradigm was utilized to examine the role of macrophages in the remodeling process following implantation of 14 biologically derived surgical mesh materials in the rat abdominal wall. In situ polarization of macrophages responding to the materials was examined and correlated to a quantitative measure of the observed tissue remodeling response to determine whether macrophage polarization is an accurate predictor of the ability of a biologic scaffold to promote constructive tissue remodeling. Additionally the ability of M1 and M2 macrophages to differentially recruit progenitor-like cells in vitro, which are commonly observed to participate in the remodeling of those ECM scaffolds which have a positive clinical outcome, was examined as a possible mechanism underlying the differences in the observed remodeling responses. The results of the present study show that there is a strong correlation between the early macrophage response to implanted materials and the outcome of tissue remodeling. Increased numbers of M2 macrophages and higher ratios of M2:M1 macrophages within the site of remodeling at 14 days were associated with more positive remodeling outcomes (r(2)=0.525-0.686, p<0.05). Further, the results of the present study suggest that the constructive remodeling outcome may be due to the recruitment and survival of different cell populations to the sites of remodeling associated with materials that elicit an M1 vs. M2 response. Both M2 and M0 macrophage conditioned media were shown to have higher chemotactic activities than media conditioned by M1 macrophages (p<0.05). A more thorough understanding of these issues will logically influence the design of next generation biomaterials and the development of regenerative medicine strategies for the formation of functional host tissues.

Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

Photomicrographs of hematoxylin and eosin stained slides showing examples of the host remodeling response to test articles in Group 1 (Collamend), Group 2 (InteXen) and Group 3 (MatriStem) at 14 (A) and 35 days (B). Scale bars = 100 μm. Images with higher magnification represent the area within the black box in lower magnification images.

Figure 2

Figure 2

Quantitative histologic scores at 14 days (A) and 35 days (B) post-implantation. Data are presented as the mean for each sample type (n=2). White bars represent materials from Group 1, grey bars represent materials from Group 2, and black bars represent materials from Group 3. Higher scores are more indicative of a constructive remodeling response while low scores are more indicative of a scar tissue or foreign body type response.

Figure 3

Figure 3

Immunofluorescent images showing examples of the host macrophage response to mesh materials from Group 1 (Collamend, A), Group 2 (InteXen, B) and Group 3 (MatriStem, C) at 14 days post implantation. Scale bar = 100 μm. CD68 (pan-macrophage) = red, CCR7 (M1) = orange, CD206 (M2) = green, DRAQ5 (nuclei) = blue.

Figure 4

Figure 4

Average number of macrophages expressing markers indicative of M0, (A,E), M1 (B,F) and M2 (C,G) polarization per high power microscope field as well as the ratio of M2:M1 marker expressing cells (D,H) at 14 days (A–D) and 35 days (E–H). Quantitative results presented as the mean for each sample type (n=2). White bars represent materials from Group 1, grey bars represent materials from Group 2, and black bars represent materials from Group 3.

Figure 5

Figure 5

Photomicrographs showing representative Boyden chamber assay results obtained using M0, M1, and M2 macrophage conditioned media (A). Quantification of C2C12 myoblast migration towards culture supernatants from M0, M1, and M2 macrophages at 4, 8, 12, and 24 hours post-implantation (B). White bar represents migration towards M0 supernatants, grey bar represents migration towards M1 supernatants, and black bar represents migration towards M2 supernatants. Scale bar = 100 μm. * denotes significance as compared to M1 with p<0.05.

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