Modulating Innate Inflammatory Reactions in the Application of Orthopedic Biomaterials

  • Tzuhua Lin
  • Eemeli Jämsen
  • Laura Lu
  • Karthik Nathan
  • Jukka Pajarinen
  • Stuart B. GoodmanEmail author


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.


Orthopedic biomaterials Inflammation Macrophage polarization Immunomodulation Wear particles Osteolysis Bone remodeling Tissue engineering Mesenchymal stem cell Osteoblast Osteoclast NF-kB 



C-C motif chemokine ligand 2


Foreign-body giant cell


Granulocyte macrophage colony-stimulating factor


Interferon gamma






Macrophage colony-stimulating factor


Mesenchymal stem cell






Pathogen-associated molecular pattern


Platelet-derived growth factor








Pattern-recognition receptor


Receptor-activator of NF-κB ligand


RNA interference


Transforming growth factor-β


Toll-like receptor


Tumor necrosis factor-α


Vascular endothelial growth factor



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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Tzuhua Lin
    • 1
  • Eemeli Jämsen
    • 1
  • Laura Lu
    • 1
  • Karthik Nathan
    • 1
  • Jukka Pajarinen
    • 1
  • Stuart B. Goodman
    • 1
    • 2
    Email author
  1. 1.Departments of Orthopedic SurgeryStanford University School of MedicineRedwood CityUSA
  2. 2.Department of BioengineeringStanford UniversityStanfordUSA

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