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Phenotypic dichotomies in the foreign body reaction
Open accessAbstract
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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“While the specific mode of failure is highly context dependent, a major complication following the implantation of any material is the development of a foreign body reaction (FBR).”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [141]
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Metadata
- Authors
- Anderson, J. M., & Jones, J. A.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Anderson, James M.
- ORCID
- Anderson, James M.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 28
- Issue
- 34
- Pages
- 5114-5120
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2248374
- OpenAlex
- W2023878656
- Cited by
- 110
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 11 · 2015: 8 · 2014: 9 · 2013: 7 · 2012: 6
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (R01EB000279, R37EB000275, EB 000275, R01EB000282, R01EB000275)
- Topics
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- foreign body reaction, macrophage activation, foreign body giant cells, hydrophobic surfaces, hydrophilic surfaces, cytokine production, IL-10, M1 macrophages, M2 macrophages, macrophage phenotype switching, cell adhesion, biocompatibility, wound healing
- MeSH terms
- Animals, Biocompatible Materials, Cell Adhesion, Enzyme-Linked Immunosorbent Assay, Foreign-Body Reaction, Humans, Macrophage Activation, Macrophages, Materials Testing, Monocytes, Phenotype, Wound Healing, Giant Cells, Giant Cells, Foreign-Body, Cytokines
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