Persistent glycolysis defines the foreign body response to polymeric implants Article Swipe
Christian N. Rempe
,
Neal I. Callaghan
,
Lauren Fong-Hollohan
,
Sarah Nersesian
,
Zachary S.C.S. Froom
,
Kyle Medd
,
Ibrahim Ahmed
,
Tobias K. Karakach
,
Jeanette E. Boudreau
,
Michael Bezuhly
,
Locke Davenport Huyer
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.02.04.636531
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.02.04.636531
Non-degradable polymeric implantable medical devices are a mainstay of modern healthcare but can frequently lead to severe complications. These complications are largely attributable to the foreign body response ( FBR ), which is characterized by excessive inflammation and fibrosis in response to implanted materials. The pathologic mechanisms underpinning the FBR remain elusive; however, metabolism is increasingly regarded as a critical regulator of innate immune function. We conducted comprehensive metabolic profiling of implant-associated macrophages and multinucleated giant cells in response to the subcutaneous implantation of clinically relevant implantable materials in a mouse model of implant fibrosis. Leveraging novel metabolic characterization methods for analysis of both metabolic dependence and enzyme expression in heterogeneous peri-implant tissues, we demonstrate that peri-implant macrophages are glycolytic at least up to six weeks post-implantation. Glycolytically dependent peri-implant macrophages’ expression of glucose transporter 1 (GLUT1) increased temporally and with proximity to the implant-tissue interface. Paired rate-limiting metabolic enzyme expression analysis showed notable increases in biosynthetic pathways (G6PD and ACC1), matched with increased mitochondrial staining intensity in GLUT1 Hi cells at chronic timepoints, which were not notable at early timepoints. Notably, we identified a glycolytic dependence of multinucleated macrophages associated with polymeric materials: these cells expressed higher levels of GLUT1 than mononuclear macrophages of comparable metabolic phenotype. Our findings highlight GLUT1-dependent glycolysis as the definitive metabolic system used by peri-implant macrophages and multinucleated cells in the FBR, highlighting this pathway as a potential target for the development of novel therapeutic approaches.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.02.04.636531
- OA Status
- green
- References
- 73
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
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- DOI
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https://doi.org/10.1101/2025.02.04.636531Digital Object Identifier
- Title
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Persistent glycolysis defines the foreign body response to polymeric implantsWork title
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-02-08Full publication date if available
- Authors
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Christian N. Rempe, Neal I. Callaghan, Lauren Fong-Hollohan, Sarah Nersesian, Zachary S.C.S. Froom, Kyle Medd, Ibrahim Ahmed, Tobias K. Karakach, Jeanette E. Boudreau, Michael Bezuhly, Locke Davenport HuyerList of authors in order
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https://doi.org/10.1101/2025.02.04.636531Publisher landing page
- Open access
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://doi.org/10.1101/2025.02.04.636531Direct OA link when available
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Glycolysis, Foreign body, Business, Medicine, Internal medicine, Surgery, MetabolismTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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