Phenotypic changes in bone marrow-derived murine macrophages cultured on PEG-based hydrogels activated or not by lipopolysaccharide
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Macrophages are phenotypically diverse cells performing a number of functions involved in immunity, inflammation, wound healing, tissue homeostasis and the foreign body reaction. In the latter, the type of biomaterial and the surrounding environment likely have an impact on macrophage phenotype and, subsequently, the severity of the reaction. The objectives for this study were to characterize the phenotype of bone marrow-derived murine macrophages in response to poly(ethylene glycol) (PEG)-based hydrogels, a promising class of materials for cell delivery. Gene expression was used as a measure of phenotype and characterized by IL-1β, TNF-α, iNOS, IL-12β, arginase, VEGF-A, and IL-10. Macrophages were cultured on PEG hydrogels, PEG hydrogels with RGD tethers, and medical grade silicone rubber, a well-characterized biomaterial, up to 96 h in the absence and presence of lipopolysaccharide (LPS) to simulate an inflammatory environment. Macrophage interrogation led to immediate up-regulation (10×) of IL-1β and TNF-α within 4h, followed by an increase in IL-10/IL-12β and a subsequent concomitant decrease in the pro-inflammatory genes by 96 h, suggesting a shift from classically activated to a regulatory phenotype. LPS stimulation led to a stronger early up-regulation of pro-inflammatory genes (e.g. 20-30× for IL-1β and TNF-α), followed by upregulation (4-6×) of arginase, suggesting a shift from an elevated classically activated to a wound healing phenotype. Material type played a significant role in regulating pro-inflammatory genes, which was most pronounced with PEG alone. Overall, our findings indicate that macrophages undergo similar phenotypic changes for the materials tested, but the magnitudes of these responses are highly material dependent.
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The authors previously reported that macrophages stimulated by LPS shift to a wound healing phenotype, but this shift was not apparent until 48 hours.
“We have previously reported that macrophages after being stimulated by LPS shift to a wound healing phenotype but this shift was not apparent until 48 hours.50”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [50]
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Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
Foreign body reaction to biomaterials
Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.004 · Cited by 5,138 · cited 1× · see citing works
“Macrophages also play a key role in orchestrating the foreign body reaction [1,2], a series of”
BackgroundMacrophage activation and polarization
Martinez, F. O. (2008) · Frontiers in Bioscience · doi:10.2741/2692 · Cited by 3,160 · see citing works
Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., & Gusovsky, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10689 · Cited by 1,924 · see citing works
The many faces of macrophage activation
Mosser, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602325 · Cited by 1,902 · see citing works
Inferences, questions and possibilities in Toll-like receptor signalling
Beutler, B. (2004) · Nature · doi:10.1038/nature02761 · Cited by 1,458 · see citing works
The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum.
(1975) · PubMed Central · Cited by 1,437 · see citing works
Biochemical and functional characterization of three activated macrophage populations
Edwards, J. P., Zhang, X., Frauwirth, K. A., & Mosser, D. M. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0406249 · Cited by 863 · see citing works
Johnston, R. B. (1988) · New England Journal of Medicine · doi:10.1056/nejm198803243181205 · Cited by 697 · see citing works
Yang, F., Williams, C. G., Wang, D., Lee, H., Manson, P. N., & Elisseeff, J. H. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.03.018 · Cited by 458 · see citing works
Molecular basis of biomaterial-mediated foreign body reactions
Hu, W.-J., Eaton, J. W., Ugarova, T. P., & Tang, L. (2001) · Blood · doi:10.1182/blood.v98.4.1231 · Cited by 431 · cited 1× · see citing works
“Protein adsorption onto the material surface may occur from the serum in vitro or from the exudate during implantation in vivo and is highly dependent on the surface characteristics of the material [32].”
BackgroundBiomaterial biocompatibility and the macrophage
Anderson, J. M., & Miller, K. M. (1984) · Biomaterials · doi:10.1016/0142-9612(84)90060-7 · Cited by 403 · see citing works
Robbins and Cotran pathologic basis of disease, 7th ed.
Kumar, V. (2005) · Cited by 400 · see citing works
Cooke, J. P., & Losordo, D. W. (2002) · Circulation · doi:10.1161/01.cir.0000014928.45119.73 · Cited by 302 · see citing works
Iwamoto, M., Kurachi, M., Nakashima, T., Kim, D., Yamaguchi, K., Oda, T., Iwamoto, Y., & Muramatsu, T. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.07.007 · Cited by 273 · see citing works
Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro
Brodbeck, W. G., Nakayama, Y., Matsuda, T., Colton, E., Ziats, N. P., & Anderson, J. M. (2002) · Cytokine · doi:10.1006/cyto.2002.1048 · Cited by 268 · see citing works
Kim, J.-B., Han, A., Park, E., et al. (2007) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.30.2345 · Cited by 252 · see citing works
Christenson, E. M., Anderson, J. M., & Hiltner, A. (2004) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30067 · Cited by 219 · see citing works
Macrophage heterogeneity and tissue lipids
Gordon, S. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30992 · Cited by 207 · see citing works
Localized Immunosuppressive Environment in the Foreign Body Response to Implanted Biomaterials
Higgins, D. M., Basaraba, R. J., Hohnbaum, A. C., Lee, E. J., Grainger, D. W., & Juarrero, M. G. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080962 · Cited by 181 · see citing works
Lynn, A. D., Kyriakides, T. R., & Bryant, S. J. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32595 · Cited by 174 · see citing works
Self-citationCytokine and growth factor production by monocytes/macrophages on protein preadsorbed polymers
Bonfield, T. L., Colton, E., Marchant, R. E., & Anderson, J. M. (1992) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820260702 · Cited by 119 · see citing works
The role of iNOS in wound healing
Shi, H., Most, D., Efron, D. T., Tantry, U. S., Fischel, M. H., & Barbul, A. (2001) · Surgery · doi:10.1067/msy.2001.115837 · Cited by 118 · see citing works
Involvement of toll-like receptor 4 in the inflammatory reaction induced by hydroxyapatite particles
Grandjean-Laquerriere, A., Tabary, O., Jacquot, J. P., Richard, D., Frayssinet, P., Guenounou, M., Laurent‐Maquin, D., Laquerrière, P., & Gangloff, S. C. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.09.015 · Cited by 115 · see citing works
Phenotypic dichotomies in the foreign body reaction
Anderson, J. M., & Jones, J. A. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.07.010 · Cited by 110 · see citing works
Nicodemus, G. D., & Bryant, S. J. (2008) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2008.02.034 · Cited by 100 · see citing works
Self-citationJay, S. M., Skokos, E., Laiwalla, F., Krady, M.-M., & Kyriakides, T. R. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.061213 · Cited by 92 · see citing works
Moon, C., Han, J. R., Park, H., Hah, J.-S., & Kang, J. L. (2009) · Respiratory Research · doi:10.1186/1465-9921-10-18 · Cited by 71 · see citing works
Schmidt, D. R., & Kao, W. J. (2007) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31270 · Cited by 56 · see citing works
Lipopolysaccharide induces calcitonin gene‐related peptide in the RAW264.7 macrophage cell line
Ma, W., Dumont, Y., Vercauteren, F., & Quirion, R. (2010) · Immunology · doi:10.1111/j.1365-2567.2009.03239.x · Cited by 56 · see citing works
Altered adherent leukocyte profile on biomaterials in Toll-like receptor 4 deficient mice
Rogers, T. H., & Babensee, J. E. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.077 · Cited by 52 · see citing works
Embleton, M. J. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601103 · Cited by 51 · see citing works
In vitro activation of human monocytes by silicones
Naim, J. O., van Oss, C. J., Ippolito, K. M. L., Zhang, J.-W., Jin, L.-P., Fortuna, R., & Buehner, N. A. (1998) · Colloids and Surfaces B Biointerfaces · doi:10.1016/s0927-7765(98)00023-x · Cited by 32 · see citing works
Mason, M. N., & Mahoney, M. J. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0290 · Cited by 22 · see citing works
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Research works printed but not linked: 1
- [8]Hamilton TA Burke B Lewis CE Molecular basis of macrophage activation: from gene expression to phenotypic diversity The Macrophage 2002 73 102 Oxford University Press New York 2nd ed
Cited by
Sorted by citations
Blakney, A. K., Swartzlander, M. D., & Bryant, S. J. (2012) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34104 · Cited by 470 · see citing works
Self-citationMonocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design
Ogle, M. E., Segar, C. E., Sridhar, S., & Botchwey, E. A. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216650293 · Cited by 378 · see citing works
Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering
Rowley, A. T., Nagalla, R. R., Wang, S., & Liu, W. F. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201801578 · Cited by 193 · see citing works
Carnicer-Lombarte (2019) · doi:10.1101/829648 · Cited by 46 · see citing works
Substrate stiffness directs the phenotype and polarization state of cord blood derived macrophages
Scott, R. A., Kiick, K. L., & Akins, R. E. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.12.040 · Cited by 43 · see citing works
- Authors
- Lynn, A. D., & Bryant, S. J.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Bryant, Stephanie J.
- ORCID
- Bryant, Stephanie J.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 7
- Issue
- 1
- Pages
- 123-132
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC2967672
- OpenAlex
- W2083080528
- Cited by
- 52
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- U.S. Department of Education
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- macrophage phenotype, PEG-based hydrogels, bone marrow-derived macrophages, lipopolysaccharide, foreign body reaction, silicone rubber, pro-inflammatory gene expression, IL-1β, TNF-α, arginase, VEGF-A, regulatory macrophages, cell delivery
- MeSH terms
- Analysis of Variance, Animals, Biocompatible Materials, Cells, Cultured, Gene Expression Regulation, Lipopolysaccharides, Macrophage Activation, Macrophages, Male, Mice, Inbred C57BL, Models, Biological, Phenotype, Polyethylene Glycols, Hydrogels, Mice
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