Macrophage phenotype in response to ECM bioscaffolds
Open accessAbstract
Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (M ECM) is distinct from both the classically activated IFNγ+LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an M ECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers.
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During degradation of implanted ECM bioscaffolds, ECM components are released and promote the transition to a remodeling phase.
“What is more, it is widely accepted that during the degradation of implanted ECM bioscaffolds, ECM components are released into the environment and promote the transition to a remodeling phase [18,44,74,78].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [44]
The Methods (§3.2) describe producing ECM degradation products, and the Discussion (§4.3) reports that those products down-regulated inflammatory markers in pre-activated macrophages, consistent with constructive remodeling. The paper does not establish that implanted scaffolds release components into their surroundings or that this release causes a transition to a distinct remodeling phase. (LLM, conf=0.84)
Experimental — accuracy not yet measuredECM degradation peptides promote M2-like phenotypes in vitro and in vivo.
“promotion of M2-like phenotypes in vitro [40,44,153] and in vivo [152,154,155].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [44]
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- Authors
- Huleihel, L., Dziki, J. L., Bartolacci, J. G., Rausch, T., Scarritt, M. E., Cramer, M. C., Vorobyov, T., LoPresti, S. T., Swineheart, I. T., White, L. J., Brown, B. N., & Badylak, S. F.
- Affiliations
- University of Pittsburgh (US)
- University of Nottingham (GB)
- Corresponding author
- Badylak, Stephen F.
- ORCID
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 29
- Pages
- 2-13
- ISSN
- 1044-5323 (ISSN-L)
- PMC
- PMC5612880
- OpenAlex
- W2737628422
- Cited by
- 169
- References
- 81
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 19 · 2023: 19 · 2022: 19 · 2021: 28 · 2020: 23 · 2019: 13 · 2018: 16 · 2017: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 601 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Seminars in Immunology (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Nottingham ePrints (University of Nottingham) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (RO1DE022055)
- Department of defense (W81XWH-15-1-0026)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- macrophage phenotype, urinary bladder matrix, small intestinal submucosa, bone marrow-derived macrophages, THP-1 cells, macrophage polarization, anti-inflammatory macrophages, inflammatory macrophages, cell surface markers, tissue repair
- MeSH terms
- Animals, Biocompatible Materials, Bone Marrow Cells, Cell Differentiation, Extracellular Matrix, Humans, Macrophages, Mammals, Phenotype, Wound Healing, Biomimetics, Tissue Scaffolds
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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