Glycolytic reprogramming underlies immune cell activation by polyethylene wear particles

Chima V Maduka; Oluwatosin M Habeeb; Maxwell M Kuhnert; Maxwell Hakun; Stuart B Goodman; Christopher H Contag

doi:10.1016/j.bioadv.2023.213495

Glycolytic reprogramming underlies immune cell activation by polyethylene wear particles

Biomater Adv. 2023 Sep:152:213495. doi: 10.1016/j.bioadv.2023.213495. Epub 2023 Jun 3.

Authors

Chima V Maduka¹, Oluwatosin M Habeeb², Maxwell M Kuhnert², Maxwell Hakun², Stuart B Goodman³, Christopher H Contag⁴

Affiliations

¹ Comparative Medicine & Integrative Biology, Michigan State University, East Lansing, MI 48824, USA; Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI 48824, USA.
² Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI 48824, USA.
³ Department of Orthopedic Surgery, Stanford University, CA 94063, USA; Department of Bioengineering, Stanford University, CA 94305, USA.
⁴ Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI 48824, USA; Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI 48864, USA. Electronic address: contagch@msu.edu.

PMID: 37301057
DOI: 10.1016/j.bioadv.2023.213495

Abstract

Primary total joint arthroplasties (TJAs) are widely and successfully applied reconstructive procedures to treat end-stage arthritis. Nearly 50 % of TJAs are now performed in young patients, posing a new challenge: performing TJAs which last a lifetime. The urgency is justified because subsequent TJAs are costlier and fraught with higher complication rates, not to mention the toll taken on patients and their families. Polyethylene particles, generated by wear at joint articulations, drive aseptic loosening by inciting insidious inflammation associated with surrounding bone loss. Down modulating polyethylene particle-induced inflammation enhances integration of implants to bone (osseointegration), preventing loosening. A promising immunomodulation strategy could leverage immune cell metabolism, however, the role of immunometabolism in polyethylene particle-induced inflammation is unknown. Our findings reveal that immune cells exposed to sterile or contaminated polyethylene particles show fundamentally altered metabolism, resulting in glycolytic reprogramming. Inhibiting glycolysis controlled inflammation, inducing a pro-regenerative phenotype that could enhance osseointegration.

Keywords: Glycolytic reprogramming; Immune cells; Polyethylene wear particles; Total joint arthroplasty.

MeSH terms

Humans
Inflammation*
Polyethylene* / adverse effects
Prostheses and Implants

Substances

Polyethylene