Physical and mechanical regulation of macrophage phenotype and function
Open accessAbstract
Macrophages are tissue-resident immune cells that play a critical role in maintaining homeostasis and fighting infection. In addition, these cells are involved in the progression of many pathologies including cancer and atherosclerosis. In response to a variety of microenvironmental stimuli, macrophages can be polarized to achieve a spectrum of functional phenotypes. This review will discuss some emerging evidence in support of macrophage phenotypic regulation by physical and mechanical cues. As alterations in the physical microenvironment often underlie pathophysiological states, an understanding of their effects on macrophage phenotype and function may help provide mechanistic insights into disease pathogenesis.
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Polyacrylamide hydrogels have been used to mimic ECMs due to their suitable mechanical strength, biocompatibility, and adjustable physicochemical properties for cell culture.
“The polyacrylamide hydrogels have been used to mimic ECMs, due to its suitable mechanical strength, biocompatibility and adjustable physicochemical properties for cell culture [20].”
From Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway (2020) · cites this paper as [20]
The Mechanical effects section (page not provided) describes culturing macrophages on polyacrylamide gels with different stiffnesses and surface modifications, supporting their use as adjustable cell-culture substrates. The copy does not establish that polyacrylamide hydrogels mimic ECMs because of suitable mechanical strength or biocompatibility. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMechanical and topographic properties of decellularized tissues are critical players in the host immune response against implanted dECM scaffolds.
“Over and above that, mechanical and topographic properties of decellularized tissues are critical players in the host immune response against implanted dECM scaffolds.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [193]
The Mechanical effects section says stiffness affects the host response to implanted biomaterials, and the Substrate topography and matrix architecture section describes how surface structure affects macrophage activation and foreign-body responses. The examples concern primarily engineered or synthetic materials, however; the paper does not establish these effects specifically for implanted decellularized tissue or dECM scaffolds. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAlteration in dECM natural conditions may affect macrophage polarization, degradation process, and FBR incidence.
“Alteration in dECM natural conditions may affect macrophage polarization, degradation process, and FBR incidence [193].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [193]
The Introduction and Concluding remarks say that ECM properties and other physical cues may affect macrophage polarization. The Substrate topography and matrix architecture section also links material properties and macrophage polarization to the foreign body response. The passages do not address altered decellularized ECM (dECM), its degradation process, or whether such alterations change FBR incidence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe mechanical properties of biomaterials, particularly stiffness, influence macrophage activation and the foreign body response.
“The mechanical properties of biomaterials, particularly stiffness, have been shown to influence macrophage activation and FBR.”
From Soft tissue-mimicking hydrogel stiffness modulates polarisation of human monocyte-derived macrophages (2025) · cites this paper as [11]
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“Due to the more complicated microenvironment in vivo, modulation of macrophage phenotype represents a critical determinant of functional and the failure of implanted biomaterials [20].”
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- Authors
- McWhorter, F. Y., Davis, C. T., & Liu, W. F.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Liu, Wendy F.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2014-12-12
- Volume
- 72
- Issue
- 7
- Pages
- 1303-1316
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC4795453
- OpenAlex
- W2096147603
- Cited by
- 437
- References
- 17
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 41 · 2023: 38 · 2022: 49 · 2021: 71 · 2020: 50 · 2019: 50 · 2018: 37 · 2017: 27 · 2016: 11 · 2015: 4
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Dental and Craniofacial Research (DP2DE023319)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD060555)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- macrophages, macrophage polarization, macrophage phenotype, physical cues, mechanical cues, extracellular matrix, tissue microenvironment, macrophage function, cancer, atherosclerosis
- MeSH terms
- Humans, Macrophages, Models, Biological, Neoplasms, Physical Stimulation, Stress, Mechanical, Mechanotransduction, Cellular, Cell Shape, Atherosclerosis, Cellular Microenvironment
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