Biodegradable magnesium materials regulate ROS-RNS balance in pro-inflammatory macrophage environment
Open accessAbstract
The relationship between reactive oxygen and nitrogen species (ROS-RNS) secretion and the concomitant biocorrosion of degradable magnesium (Mg) materials is poorly understood. We found that Mg foils implanted short term in vivo (24 h) displayed large amounts of proinflammatory F4/80+/iNOS + macrophages at the interface. We sought to investigate the interplay between biodegrading Mg materials (98.6% Mg, AZ31 & AZ61) and macrophages (RAW 264.7) stimulated with lipopolysaccharide (RAW 264.7LPS) to induce ROS-RNS secretion. To test how these proinflammatory ROS-RNS secreting cells interact with Mg corrosion in vitro, Mg and AZ61 discs were suspended approximately 2 mm above a monolayer of RAW 264.7 cells, either with or without LPS. The surfaces of both materials showed acute (24 h) changes when incubated in the proinflammatory RAW 264.7LPS environment. Mg discs incubated with RAW 264.7LPS macrophages showed greater corrosion pitting, while AZ61 showed morphological and elemental bulk product changes via scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX). X-ray photoelectron spectroscopy (XPS) analysis showed a reduction in the Ca/P ratio of the surface products for AZ61 disc incubated with RAW 264.7LPS, but not the Mg discs. Moreover, RAW 264.7LPS macrophages were found to be more viable in the acute biodegradative environment generated by Mg materials, as demonstrated by calcein-AM and cleaved (active) caspase-3 staining (CC3). LPS stimulation caused an increase in ROS-RNS, and a decrease in antioxidant peroxidase activity. Mg and AZ61 were found to change this ROS-RNS balance, independently of physiological antioxidant mechanisms. The findings highlight the complexity of the cellular driven acute inflammatory responses to different biodegradable Mg, and how it can potentially affect performance of these materials.
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Elevated ROS levels and the localized acidic microenvironment may exacerbate the non-uniform corrosion property of Mg implants.
“Elevated ROS levels and the localized acidic microenvironment may further exacerbate the non-uniform corrosion property of Mg implants16.”
From Intelligence-responsive wettability switch coating on magnesium implants for treating osteoporotic fracture (2026) · cites this paper as [16]
The Conclusions (page not specified) report that pro-inflammatory macrophages caused more localized corrosion of Mg discs. The Discussion, under “The ROS-RNS balance in stimulated RAW264.7 cells incubated with AZ61 and Mg” (page not specified), says ROS-RNS secretion or pH regulation might contribute, but the study did not establish that elevated ROS and a localized acidic microenvironment specifically caused the non-uniform corrosion. (LLM, conf=0.85)
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- Authors
- Kwesiga, M. P., Gillette, A. A., Razaviamri, F., Plank, M. E., Canull, A. L., Alesch, Z., He, W., Lee, B. P., & Guillory, R. J.
- Affiliations
- Michigan Technological University (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Guillory, Roger J.
- ORCID
- Venue
- Bioactive Materials
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 23
- Pages
- 261-273
- ISSN
- 2097-1192 (ISSN-L)
- 2452-199X
- PMC
- PMC9678810
- OpenAlex
- W4309263885
- Cited by
- 25
- References
- 59
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 5
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bioactive Materials (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Commons - Michigan Tech (Michigan Technological University) (submittedVersion, cc-by-nc-nd)
- Language arts journal of Michigan (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (2001076, R15GM135875)
- Michigan Technological University
- National Institutes of Health (DMR 2001076)
- National Institute of General Medical Sciences (R15GM135875)
- Division of Materials Research (2001076, DMR-2001076)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Magnesium Alloys: Properties and Applications
- Physical Sciences › Materials Science › Materials Chemistry › Titanium Alloys Microstructure and Properties
- Health Sciences › Nursing › Nutrition and Dietetics › Magnesium in Health and Disease
- Keywords
- biodegradable magnesium, magnesium corrosion, reactive oxygen species, reactive nitrogen species, macrophages, lipopolysaccharide, AZ31 magnesium alloy, AZ61, pitting corrosion, calcium/phosphate ratio, macrophage viability, caspase-3, implant biocompatibility
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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