Regulating the proinflammatory response to composite biomaterials by targeting immunometabolism

Chima V. Maduka; Ashley V. Makela; Anthony Tundo; Evran Ural; Katlin B. Stivers; Maxwell M. Kuhnert; Mohammed Alhaj; Ehsanul Hoque Apu; Nureddin Ashammakhi; Kurt D. Hankenson; Ramani Narayan; Jennifer H. Elisseeff; Christopher H. Contag

Bioactive Materials (Oct 2024)

Regulating the proinflammatory response to composite biomaterials by targeting immunometabolism

Chima V. Maduka,
Ashley V. Makela,
Anthony Tundo,
Evran Ural,
Katlin B. Stivers,
Maxwell M. Kuhnert,
Mohammed Alhaj,
Ehsanul Hoque Apu,
Nureddin Ashammakhi,
Kurt D. Hankenson,
Ramani Narayan,
Jennifer H. Elisseeff,
Christopher H. Contag

Affiliations

Chima V. Maduka: Comparative Medicine & Integrative Biology, Michigan State University, East Lansing, MI, 48824, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA; Corresponding author. Comparative Medicine & Integrative Biology, Michigan State University, East Lansing, MI, 48824, USA.
Ashley V. Makela: Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA
Anthony Tundo: Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA
Evran Ural: Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA
Katlin B. Stivers: Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
Maxwell M. Kuhnert: Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA
Mohammed Alhaj: Department of Chemical Engineering & Materials Science, Michigan State University, East Lansing, MI, 48824, USA
Ehsanul Hoque Apu: Department of Biomedical Sciences, College of Dental Medicine, Lincoln Memorial University, Knoxville, TN, 37917, USA
Nureddin Ashammakhi: Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA; Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA
Kurt D. Hankenson: Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
Ramani Narayan: Department of Chemical Engineering & Materials Science, Michigan State University, East Lansing, MI, 48824, USA
Jennifer H. Elisseeff: Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
Christopher H. Contag: Department of Biomedical Engineering, College of 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, Genetics & Immunology, Michigan State University, East Lansing, MI, 48864, USA; Corresponding author. Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, 48824, USA.

Journal volume & issue: Vol. 40
pp. 64 – 73

Abstract

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Composite biomaterials comprising polylactide (PLA) and hydroxyapatite (HA) are applied in bone, cartilage and dental regenerative medicine, where HA confers osteoconductive properties. However, after surgical implantation, adverse immune responses to these composites can occur, which have been attributed to size and morphology of HA particles. Approaches to effectively modulate these adverse immune responses have not been described. PLA degradation products have been shown to alter immune cell metabolism (immunometabolism), which drives the inflammatory response. Accordingly, to modulate the inflammatory response to composite biomaterials, inhibitors were incorporated into composites comprised of amorphous PLA (aPLA) and HA (aPLA + HA) to regulate glycolytic flux. Inhibition at specific steps in glycolysis reduced proinflammatory (CD86+CD206-) and increased pro-regenerative (CD206+) immune cell populations around implanted aPLA + HA. Notably, neutrophil and dendritic cell (DC) numbers along with proinflammatory monocyte and macrophage populations were decreased, and Arginase 1 expression among DCs was increased. Targeting immunometabolism to control the proinflammatory response to biomaterial composites, thereby creating a pro-regenerative microenvironment, is a significant advance in tissue engineering where immunomodulation enhances osseointegration and angiogenesis, which could lead to improved bone regeneration.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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