SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions

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dc.citation.articleNumber189
dc.citation.issueNumber2
dc.citation.journalTitleAntioxidants
dc.citation.volumeNumber13
dc.contributor.authorAhuja, Neelam
dc.contributor.authorAwad, Kamal
dc.contributor.authorYang, Su
dc.contributor.authorDong, He
dc.contributor.authorMikos, Antonios
dc.contributor.authorAswath, Pranesh
dc.contributor.authorYoung, Simon
dc.contributor.authorBrotto, Marco
dc.contributor.authorVaranasi, Venu
dc.contributor.orgCenter for Engineering Complex Tissues
dc.contributor.orgCenter for Excellence in Tissue Engineering
dc.date.accessioned2024-07-25T20:56:27Z
dc.date.available2024-07-25T20:56:27Z
dc.date.issued2024
dc.description.abstractHealing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiONx) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiONx to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of SiONx coatings on osteogenesis with and without toxic oxidative stress. Additionally, bacterial growth on SiONx surfaces was studied using methicillin-resistant Staphylococcus aureus (MRSA) colonies. NRF2 siRNA transfection was performed on the hMSCs (NRF2-KD) to study the antioxidant response to silicon ions. The SiONx implant surfaces showed a >4-fold decrease in bacterial growth vs. bare titanium as a control. Increasing the N/O ratio in the SiONx implants increased the alkaline phosphatase activity >1.5 times, and the other osteogenic markers (osteocalcin, RUNX2, and Osterix) were increased >2-fold under normal conditions. Increasing the N/O ratio in SiONx enhanced the protective effects and improved cell viability against toxic oxidative stress conditions. There was a significant increase in osteocalcin activity compared to the uncoated group, along with increased antioxidant activity under oxidative stress conditions. In NRF2-KD cells, there was a stunted effect on the upregulation of antioxidant markers by silicon ions, indicating a role for NRF2. In conclusion, the SiONx coatings studied here displayed bacteriostatic properties. These materials promoted osteogenic markers under toxic oxidative stress conditions while also enhancing antioxidant NRF2 activity. These results indicate the potential of SiONx coatings to induce in vivo bone regeneration in a challenging oxidative stress environment.
dc.identifier.citationAhuja, N., Awad, K., Yang, S., Dong, H., Mikos, A., Aswath, P., Young, S., Brotto, M., & Varanasi, V. (2024). SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions. Antioxidants, 13(2), Article 2. https://doi.org/10.3390/antiox13020189
dc.identifier.digitalantioxidants-13-00189
dc.identifier.doihttps://doi.org/10.3390/antiox13020189
dc.identifier.urihttps://hdl.handle.net/1911/117538
dc.language.isoeng
dc.publisherMDPI
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleSiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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