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Modulating Innate Inflammatory Reactions in the Application of Orthopedic Biomaterials

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Orthopedic Biomaterials

Abstract

Orthopaedic biomaterials are used in a wide variety of surgical procedures including total joint replacement, spine reconstruction, and fracture repair. Despite the development of materials with enhanced mechanical and biological properties, the attachment of an implant to the surrounding bone is still occasionally lost and revision surgery is required in some of the patients with prolonged implantation of orthopaedic biomaterials. The macrophage-associated innate immune response plays a crucial role both in the successful integration and potential rejection of the implant. Acute inflammation is essential for the successful osseointegration and bone regeneration around the implants. Chronic inflammation, on the other hand, is associated with impaired bone formation and osteolysis in the presence of excessive macrophage infiltration and pro-inflammatory cytokine secretion. Here we summarize the current development of immunomodulating strategies to improve the application of orthopaedic biomaterials. The potential drug delivery and controlled release methods that could be applied to administrate immunomodulatory biomolecules are also discussed. In summary, modulations of the innate immune response with the goal of sequential transition from a pro-inflammatory to an anti-inflammatory reaction provides a promising strategy for successful bone regeneration and implant osseointegration.

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Abbreviations

CCL2:

C-C motif chemokine ligand 2

FBGC:

Foreign-body giant cell

GM-CSF:

Granulocyte macrophage colony-stimulating factor

IFN-γ:

Interferon gamma

IL:

Interleukin

LPS:

Lipopolysaccharide

M-CSF:

Macrophage colony-stimulating factor

MSC:

Mesenchymal stem cell

ODN:

Oligodeoxynucleotide

OPG:

Osteoprotegerin

PAMP:

Pathogen-associated molecular pattern

PDGF:

Platelet-derived growth factor

PGA:

Poly-glycolic-acid

PLA:

Poly-lactic-acid

PLGA:

Poly-lactic-glycolic-acid

PRR:

Pattern-recognition receptor

RANKL:

Receptor-activator of NF-κB ligand

RNAi:

RNA interference

TGF-β:

Transforming growth factor-β

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

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Acknowledgement

This work was supported by NIH grants 2R01AR055650, 1R01AR063717 and the Ellenburg Chair in Surgery at Stanford University. J. P. was supported by a grant from the Jane and Aatos Erkko foundation.

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Departments of Orthopedic Surgery, Stanford University School of Medicine, Redwood City, CA, USA

    Tzuhua Lin, Eemeli Jämsen, Laura Lu, Karthik Nathan, Jukka Pajarinen & Stuart B. Goodman

  2. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Stuart B. Goodman

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  1. Tzuhua Lin
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  2. Eemeli Jämsen
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  3. Laura Lu
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  4. Karthik Nathan
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  5. Jukka Pajarinen
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  6. Stuart B. Goodman
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Correspondence to Stuart B. Goodman .

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Editors and Affiliations

  1. Department of Orthopedics School of Medicine, West Virginia University, Morgantown, West Virginia, USA

    Bingyun Li

  2. Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, USA

    Thomas Webster

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Lin, T., Jämsen, E., Lu, L., Nathan, K., Pajarinen, J., Goodman, S.B. (2018). Modulating Innate Inflammatory Reactions in the Application of Orthopedic Biomaterials. In: Li, B., Webster, T. (eds) Orthopedic Biomaterials . Springer, Cham. https://doi.org/10.1007/978-3-319-89542-0_10

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