Inflammation and wound healing: the role of the macrophage
Open accessAbstract
The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have many functions in wounds, including host defence, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound and that the influence of these cells on each stage of repair varies with the specific phenotype. Although the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation or fibrosis under certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of nonhealing and poorly healing wounds. As a result of advances in the understanding of this multifunctional cell, the macrophage continues to be an attractive therapeutic target, both to reduce fibrosis and scarring, and to improve healing of chronic wounds.
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Macrophages belong to active innate immune cells and provide important responses following interaction with a biomaterial, including proteins, interleukins, chemokines, and immunomodulatory factors that steer the environment toward a pro- or anti-inflammatory state.
“Macrophages belong to the group of active innate immune cells and provide some of the most important responses following the interaction with a biomaterial. These responses include a number of proteins, interleukins, chemokines, and immunomodulatory factors that steer the environment toward either a pro‐ or anti‐inflammatory state.[ 64 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [64]
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Experimental — accuracy not yet measuredMacrophages regulate ECM content and remodeling by secretion of proteases and inhibitors, such as MMPs and TIMPs.
“In the final phase of healing, macrophages also regulate ECM content and remodeling by secretion of proteases and their inhibitors, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) [75–77].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [75]
The section on angiogenesis, fibroblast proliferation and ECM synthesis says macrophages produce proteases and inhibitors that influence ECM content and remodeling. It does not identify MMPs or TIMPs. The section on macrophage phenotypes describes their role in the final resolution phase as an open question, so the source does not establish the claim specifically for that phase. (LLM, conf=0.85)
Experimental — accuracy not yet measuredM2 macrophages consistently express scavenger and mannose receptors (CD206), release anti-inflammatory cytokines such as IL-10, display high iron export aiding tissue remodeling, and encompass subsets including wound healing and regulatory macrophages.
“M2 macrophages consistently express scavenger and mannose receptors (CD206), release anti-inflammatory cytokines such as IL-10 [19], display a high level of iron export aiding in tissue remodeling [18] and encompass a range of different subsets (i.e., M2a, M2b, M2c) including 'wound healing' and 'regulatory macrophages' [20].”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [19]
Macrophages are recognized as the most long-lived and central cell population in dermal wound healing, largely through production of cytokines, growth factors, and MMPs.
“Macrophages, however, have been recognized as the most long-lived and central cell population that plays a role in dermal wound healing largely through the production of the cytokines, growth factors, and MMPs described above [93,103,104].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [103]
The key cells of the inflammatory phase are neutrophils and monocytes/macrophages.
“The key cells of the inflammatory phase are neutrophils and monocytes/macrophages [2, 6, 45].”
From The role of the extracellular matrix components in cutaneous wound healing (2014) · cites this paper as [45]
Macrophages play a critical role in wound healing, including in angiogenesis, fibroplasia, cell proliferation, and transition out of the inflammatory phase.
“Macrophages play a critical role in wound healing, and their roles in angiogenesis, fibroplasia, cell proliferation, and transition out of the inflammatory phase is clear (Fig. 2) [25–27, 60].”
From Immunology of Wound Healing (2018) · cites this paper as [60]
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- Authors
- Koh, T. J., & DiPietro, L. A.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- DiPietro, Luisa Ann
- Venue
- Expert Reviews in Molecular Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2011-07
- Volume
- 13
- Pages
- e23-e23
- ISSN
- 1462-3994 (ISSN-L)
- PMC
- PMC3596046
- OpenAlex
- W2028543411
- Cited by
- 1,667
- References
- 69
- Citations by year
- 2026: 109 · 2025: 124 · 2024: 164 · 2023: 138 · 2022: 176 · 2021: 168 · 2020: 174 · 2019: 172 · 2018: 137 · 2017: 100 · 2016: 67 · 2015: 52 · 2014: 43 · 2013: 24 · 2012: 14
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Expert Reviews in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p20gm078426-04)
- U.S. Army (W81XWH)
- National Institute of General Medical Sciences (R01-GM-50875, R01GM050875, P20‐GM078426)
- Medical Research and Materiel Command
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- macrophages, wound healing, inflammation, macrophage phenotype, chronic wounds, fibrosis, scar formation, efferocytosis, host defense, macrophage dysfunction, therapeutic target
- MeSH terms
- Hypoxia, Fibrosis, Humans, Inflammation, Leukocytes, Macrophages, Wound Healing, Apoptosis, Neovascularization, Physiologic, Intercellular Signaling Peptides and Proteins, Cell Proliferation
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