Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component

Abstract

Recently, macrophages have been characterized as having an M1 or M2 phenotype based on receptor expression, cytokine and effector molecule production, and function. The effects of macrophage phenotype upon tissue remodeling following the implantation of a biomaterial are largely unknown. The objectives of this study were to determine the effects of a cellular component within an implanted extracellular matrix (ECM) scaffold upon macrophage phenotype, and to determine the relationship between macrophage phenotype and tissue remodeling. Partial-thickness defects in the abdominal wall musculature of Sprague–Dawley rats were repaired with autologous body wall tissue, acellular allogeneic rat body wall ECM, xenogeneic pig urinary bladder tissue, or acellular xenogeneic pig urinary bladder ECM. At 3, 7, 14, and 28 days the host tissue response was characterized using histologic, immunohistochemical, and RT-PCR methods. The acellular test articles were shown to elicit a predominantly M2 type response and resulted in constructive remodeling, while those containing a cellular component, even an autologous cellular component, elicited a predominantly M1 type response and resulted in deposition of dense connective tissue and/or scarring. We conclude that the presence of cellular material within an ECM scaffold modulates the phenotype of the macrophages participating in the host response following implantation, and that the phenotype of the macrophages participating in the host response appears to be related to tissue remodeling outcome.

Polymer-Based Reconstruction of the Inferior Vena Cava in Rat: Stem Cells or RGD Peptide?

“…From this standpoint, PDO and PHVBB outperformed PU with regard to the predominance of infiltrating regulatory ED2 macrophages, a phenotype associated with less inflammatory tissue scarring and improved remodelling. 35,36 The enhanced ED2 response to PDO and PHBVV is consistent with our concurrent findings of higher expressions of the anti-inflammatory IL-10 cytokine and MCP-1 chemokine. In contrast, PU was associated with a much greater inflammatory response, with a persisting insulation of the patches and, occasionally, granulomas, which have also been reported in other applications.…”

Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response

“…As both inflammatory and anti-inflammatory cytokine genes are triggered by LPS and IL-4 (as prototypes of type 1 and type 2 inflammation), the relative activation of inflammatory vs antiinflammatory genes is a better estimate of M1 vs M2 polarization as compared to assessement of single genes. The ratio of M1:M2 cells may be more important than the absolute number [31] . M1 macrophage cells usually have the phenotype showing IL-12 high, IL-10 low, IL-23 high, and M2 cells vice versa [32] .…”

Injectable Acellular Hydrogels for Cardiac Repair

“…Radiesse was injected into the myocardium 45 min after ligation in an ovine MI model and analyzed at 4 weeks; injection resulted in a thickened myocardial wall, increased global EF, and reduced LV end systolic volumes compared to controls. Unlike the previously mentioned hydrogel systems that directly bulk the myocardium through hydrogel crosslinking, this approach provides an effective means to induce tissue bulking by promoting the biological response to materials for attenuated LV remodeling and preserved cardiac function [72][73][74][75][76][77].…”