Phenotypic dichotomies in the foreign body reaction - PubMed (original) (raw)

Phenotypic dichotomies in the foreign body reaction

James M Anderson et al. Biomaterials. 2007 Dec.

Abstract

To better understand the relationship between macrophage/foreign body giant cell adhesion and activation on surface-modified biomaterials, quantitative assessment of adherent cell density (cells per mm(2)) and cytokine production (pgs per mL) were determined by ELISA. Further analysis to identify cellular activation was carried out by normalizing the cytokine concentration data to provide a measure of cellular activation. This method of analysis demonstrated that hydrophobic surfaces provided statistically significantly greater adherent cell densities than hydrophilic/neutral surfaces. However, when cell activation parameters were determined by normalization to the adherent cell density, the hydrophilic/neutral surfaces demonstrated statistically significantly greater levels of activation and production of IL-10, IL-1beta, IL-6, IL-8, and MIP-1beta. With increasing time, production of the anti-inflammatory cytokine IL-10 increased, whereas IL-1beta, IL-6, and IL-8 decreased and MIP-1beta was relatively constant over the culture time period. This observed dichotomy or disparity between adhesion and activation may be related to surface-induced adherent cell apoptosis. Further evaluation of macrophage activation on biomaterial surfaces indicated that an apparent phenotypic switch in macrophage phenotype occurred over the course of the in vitro culture. Analysis of cytokine/chemokine profiles with surface-modified biomaterials revealed similarities between the classically activated macrophages and the biomaterial-adherent macrophages early (day 3) in culture, while at later timepoints the biomaterial-adherent macrophages produced profiles similar to alternatively activated macrophages. Classically activated macrophages are those commonly activated by lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma) and alternatively activated macrophages are those activated by IL-4/IL-13 or IL-10. Surface modification of biomaterials offer an opportunity to control cellular activation and cytokine profiles in the phenotypic switch, and may provide a means by which macrophages can be induced to regulate particular secretory proteins that direct inflammation, the foreign body reaction, wound healing, and ultimately biocompatibility.

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Figures

Figure 1

Figure 1. Disparate Effects of Hydrophobic and Hydrophilic Surfaces on Macrophage Adhesion (A) and Fusion (B)

Numerical notations are the ratio of the data for PAAm surfaces to the data for BDEDTC surfaces. Mean ± SEM, n=3. “*” indicates a statistical difference between values (p<0.05).

Figure 2

Figure 2. Disparate Effects of Hydrophilic Non-Ionic and Ionic Surfaces on Macrophage Adhesion (A) and Fusion (B)

Numerical notations are the ratio of the data for PAAm surfaces to the data for either the PAANa or DMAPAAmMeI surfaces. Mean ± SEM, n=3. “*” indicates a statistical difference between values (p<0.05).

Figure 3

Figure 3. Direct Comparison of Cellular Adhesion (A), Cytokine Concentration (B), and Cellular Activation (C) on Hydrophobic and Hydrophilic/Neutral Surfaces

Cellular activation equals cytokine concentration (pg/mL) measured in 1mL of media normalized to the total number of adherent cells (cells/mm²). Mean ± SEM, n=3,4. “*” indicates that a statistical difference between values (p<0.05).

Figure 4

Figure 4. Cytokine/Chemokine Concentration (A–D) and Cellular Activation (E–H) on Hydrophobic and Hydrophilic/Neutral Surfaces

Cellular activation equals cytokine concentration (pg/mL) measured in 1mL of media normalized to the total number of adherent cells (cells/mm²). Mean ± SEM, n=3,4. “*” indicates that a statistical difference between values (p<0.05).

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