Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials
Open accessAbstract
Macrophages have been classified as having plastic phenotypes which exist along a spectrum between M1 (classically activated; pro-inflammatory) and M2 (alternatively activated; regulatory, homeostatic). To date, the effects of polarization towards an M1 or M2 phenotype have been studied largely in the context of response to pathogen or cancer. Recently, M1 and M2 macrophages have been shown to play distinct roles in tissue remodeling following injury. In the present study, the M1/M2 paradigm was utilized to examine the role of macrophages in the remodeling process following implantation of 14 biologically derived surgical mesh materials in the rat abdominal wall. In situ polarization of macrophages responding to the materials was examined and correlated to a quantitative measure of the observed tissue remodeling response to determine whether macrophage polarization is an accurate predictor of the ability of a biologic scaffold to promote constructive tissue remodeling. Additionally the ability of M1 and M2 macrophages to differentially recruit progenitor-like cells in vitro, which are commonly observed to participate in the remodeling of those ECM scaffolds which have a positive clinical outcome, was examined as a possible mechanism underlying the differences in the observed remodeling responses. The results of the present study show that there is a strong correlation between the early macrophage response to implanted materials and the outcome of tissue remodeling. Increased numbers of M2 macrophages and higher ratios of M2:M1 macrophages within the site of remodeling at 14 days were associated with more positive remodeling outcomes (r(2)=0.525-0.686, p<0.05). Further, the results of the present study suggest that the constructive remodeling outcome may be due to the recruitment and survival of different cell populations to the sites of remodeling associated with materials that elicit an M1 vs. M2 response. Both M2 and M0 macrophage conditioned media were shown to have higher chemotactic activities than media conditioned by M1 macrophages (p<0.05). A more thorough understanding of these issues will logically influence the design of next generation biomaterials and the development of regenerative medicine strategies for the formation of functional host tissues.
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Persistent foreign material degradation can continuously activate M1 macrophages.
“Persistent foreign material degradation can continuously activate M1 macrophages.[ 39 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [39]
The Results (§4.2; page unavailable) report predominantly M1 macrophages around implanted mesh at both 14 and 35 days, supporting a sustained M1 response to foreign material. But §4.1 reports little to no degradation in that group, while rapidly degrading materials showed a different response. The paper does not establish that persistent degradation continuously activates M1 macrophages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNatural scaffolds, such as decellularized ECM, have been shown to shift macrophage polarization from M1 to M2 due to degradation of remaining biological products.
“Natural scaffolds, such as the aforementioned decellularized ECM have also been shown to shift the macrophage polarization from M1 to M2 due to degradation of remaining biological products.[ 39 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [39]
The Results and Abstract report that implanted ECM scaffolds elicited different macrophage profiles, with higher M2:M1 ratios associated with constructive remodeling. But the Discussion says the mechanism of macrophage modulation is not fully understood; it does not establish that degradation of remaining biological products causes an M1-to-M2 shift. It describes residual cellular debris as potentially detrimental instead. (LLM, conf=0.87)
Experimental — accuracy not yet measuredA high M2:M1 ratio in the vicinity of implanted biomaterials leads to better remodeling outcomes.
“Although it has been suggested that a high M2:M1 ratio in the vicinity of implanted biomaterials leads to better remodeling outcomes [32]”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [32]
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Self-citationModels of immunogenicity in preclinical assessment of tissue engineered heart valves
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Extracellular Matrix for Myocardial Repair
Dziki, J. L., & Badylak, S. F. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-97421-7_8 · Cited by 25 · see citing works
Self-citationLoPresti, S. T., Popovic, B., Kulkarni, M., Skillen, C. D., & Brown, B. N. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119376 · Cited by 24 · see citing works
Self-citationHost Response to Naturally Derived Biomaterials
Lopresti, S. T., & Brown, B. N. (2015) · Host Response to Biomaterials · doi:10.1016/b978-0-12-800196-7.00004-9 · Cited by 24 · see citing works
Self-citationMatrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis
Liao, R., Dewey, M. J., Rong, J., Johnson, S. A., D’Angelo, W. A., Hussey, G. S., & Badylak, S. F. (2024) · Science Advances · doi:10.1126/sciadv.adn1852 · Cited by 20 · see citing works
Self-citation
- Authors
- Brown, B. N., Londono, R., Tottey, S., Zhang, L., Kukla, K. A., Wolf, M. T., Daly, K. A., Reing, J. E., & Badylak, S. F.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Badylak, Stephen F.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 8
- Issue
- 3
- Pages
- 978-987
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC4325370
- OpenAlex
- W2105415546
- Cited by
- 745
- References
- 55
- Citations by year
- 2026: 21 · 2025: 39 · 2024: 47 · 2023: 44 · 2022: 49 · 2021: 71 · 2020: 67 · 2019: 54 · 2018: 65 · 2017: 62 · 2016: 55 · 2015: 64 · 2014: 57 · 2013: 35 · 2012: 12
- FWCI
- 34.08
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-07-01)
- 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 (R01 AR054940-01, F31 EB007914)
- Topics
- Health Sciences › Medicine › Surgery › Hernia repair and management
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- macrophage polarization, M1/M2 macrophages, tissue remodeling, abdominal wall, biomaterial implantation, M2 macrophages, progenitor cell recruitment, chemotaxis, macrophage-conditioned medium, regenerative medicine, biomaterial design
- MeSH terms
- Animals, Macrophage Activation, Materials Testing, Regeneration, Stem Cells, Surgical Mesh, Rats, Sprague-Dawley, Macrophages, Peritoneal, Rats
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