@article{121f660e59bd4742914e96a45334b326,
title = "Biomaterial mediated simultaneous delivery of spermine and alpha ketoglutarate modulate metabolism and innate immune cell phenotype in sepsis mouse models",
abstract = "Although different metabolic pathways have been associated with distinct macrophage phenotypes, the field of utilizing metabolites to modulate macrophage phenotype is in a nascent stage. In this report, we developed microparticles based on polymerization of alpha-ketoglutarate (a Krebs cycle metabolite), with or without encapsulation of spermine (a polyamine metabolite), to modulate cell phenotype that are critical for resolution of inflammation. Poly (alpha-ketoglutarate) microparticles encapsulated and released spermine (spermine (encap)paKG MPs) in vitro, which was accelerated in an acidic environment. When delivered to bone marrow-derived-macrophages, spermine (encap)paKG MPs induced a complex phenotypic profile outside of the typical M1/M2 paradigm, with distinct effects in the presence or absence of the pro-inflammatory stimulus lipopolysaccharide. Of particular interest was the increase in expression of CD163, which has been linked to anti-inflammatory responses in sepsis. Therefore, we systemically administered spermine (encap)paKG MPs to two different murine models of sepsis using acute or chronic injection of LPS. Macrophages and neutrophils in the liver and spleen of animals treated with spermine (encap)paKG MPs increased expression of CD163, concomitant with normalizing of glycolysis and oxidative phosphorylation, in both models. Overall, these results show that spermine (encap)paKG MPs modulate macrophage phenotype in vitro and in vivo, with potential applications in inflammation-associated diseases.",
keywords = "Biomaterials, Immunoengineering, Immunometabolism, Macrophages, Sepsis",
author = "Sahil Inamdar and Tina Tylek and Abhirami Thumsi and Suresh, {Abhirami P.} and Jaggarapu, {Madhan Mohan Chandra Sekhar} and Michelle Halim and Shivani Mantri and Arezoo Esrafili and Ng, {Nathan D.} and Elizabeth Schmitzer and Kelly Lintecum and {de {\'A}vila}, Camila and Fryer, {John D.} and Ying Xu and Spiller, {Kara L.} and Acharya, {Abhinav P.}",
note = "Funding Information: The authors would like to acknowledge funding sources to APA that supported this work - NIH R01AR078343 and NIH R01AI155907 , 1R01GM144966-01 and NSF award# 2145877 . The Ms would also like to acknowledge the Flow Cytometry Core, the FEI at Erying Materials Center, and the Department of Animal Care and Technologies at Arizona State University . Additionally, the authors would like to thank Dr. Seo, School of Molecular Sciences , Arizona State University for providing access to dynamic light scatter. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Abhinav P. Acharya reports financial support was provided by National Institutes of Health. Abhinav P. Acharya reports a relationship with Immunometabolix, LLC that includes: equity or stocks. Abhinav P. Acharya has patent issued to Arizona State University.The authors would like to acknowledge funding sources to APA that supported this work - NIH R01AR078343 and NIH R01AI155907, 1R01GM144966-01 and NSF award# 2145877. The Ms would also like to acknowledge the Flow Cytometry Core, the FEI at Erying Materials Center, and the Department of Animal Care and Technologies at Arizona State University. Additionally, the authors would like to thank Dr. Seo, School of Molecular Sciences, Arizona State University for providing access to dynamic light scatter. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",
year = "2023",
month = feb,
doi = "10.1016/j.biomaterials.2022.121973",
language = "English (US)",
volume = "293",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
}