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Porous Implants Modulate Healing and Induce Shifts in Local Macrophage Polarization in the Foreign Body Reaction

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Abstract

The foreign body reaction (FBR) to implanted materials is of critical importance when medical devices require biological integration and vascularization to support their proper function (e.g., transcutaneous devices, implanted drug delivery systems, tissue replacements, and sensors). One class of materials that improves FBR outcomes is made by sphere-templating, resulting in porous structures with uniform, interconnected 34 μm pores. With these materials we observe reduced fibrosis and increased vascularization. We hypothesized that improved healing is a result of a shift in macrophage polarization, often measured as the ratio of M1 pro-inflammatory cells to M2 pro-healing cells. In this study, macrophage polarity of 34 μm porous implants was compared to non-porous and 160 μm porous implants in subcutaneous mouse tissue. Immunohistochemistry revealed that macrophages in implant pores displayed a shift towards an M1 phenotype compared to externalized cells. Macrophages in 34 μm porous implants had up to 63% greater expression of M1 markers and up to 85% reduction in M2 marker expression (p < 0.05). Macrophages immediately outside the porous structure, in contrast, showed a significant enrichment in M2 phenotypic cells. This study supports a role for macrophage polarization in driving the FBR to implanted materials.

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Acknowledgments

These studies were funded by University of Washington Engineered Biomaterials (UWEB21). Materials support was from RTM who is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Bioengineering, University of Washington, Box 355061, William H. Foege Building, Room N330J, Seattle, WA, USA

    Eric M. Sussman, Michelle C. Halpin & Buddy D. Ratner

  2. Department of Pharmacology, University of Washington, Seattle, WA, USA

    Jeanot Muster & Randall T. Moon

  3. Department of Chemical Engineering, University of Washington, Seattle, WA, USA

    Buddy D. Ratner

  4. Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA, USA

    Jeanot Muster & Randall T. Moon

  5. Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 358056, 850 Republican Street, S525, Seattle, WA, USA

    Jeanot Muster, Randall T. Moon & Buddy D. Ratner

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  1. Eric M. Sussman
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  2. Michelle C. Halpin
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Correspondence to Buddy D. Ratner.

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Associate Editor Tzung Hsiai oversaw the review of this article.

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Sussman, E.M., Halpin, M.C., Muster, J. et al. Porous Implants Modulate Healing and Induce Shifts in Local Macrophage Polarization in the Foreign Body Reaction. Ann Biomed Eng 42, 1508–1516 (2014). https://doi.org/10.1007/s10439-013-0933-0

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