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. 2023;5(1):9-19.
doi: 10.26502/josm.511500073. Epub 2022 Dec 5.

Innate Immune Response in Orthopedic Implant Failure

Affiliations

Innate Immune Response in Orthopedic Implant Failure

Rajiv Supra et al. J Orthop Sports Med. 2023.

Abstract

The total joint replacement is recognized as one of the most effective medical arbitrations leading to increased mobility, pain relief, and an overall restored function of the joint. Unfortunately, prosthetic debris accumulates after long-term wear of the implant leading to activation of the innate immune response and periprosthetic osteolysis. Understanding the intricate biological mechanisms underlying the innate immune response to implant debris would support the development of novel pharmacological treatments to prolong the life span of the implant. This article provides a detailed description on the role of the innate immune system in response to implant debris, emphasizing the most recent research and outstanding questions. Furthermore, a critical discussion is presented on the novel pharmacological treatments currently under investigation to prevent implant failure.

Keywords: Inflammation; Innate immune response; Orthopedic implants; Prosthetic debris.

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Conflict of interest statement

Conflicts of Interest: The authors declare no conflict of interest.

Figures

Figure 1:
Figure 1:
Implant debris-induced macrophage activation and the innate immune responses leading to bone resorption, osteolysis, and implant failure. The wear debris from the implant are recognized as foreign particles that are phagocytosed by macrophages. These macrophages become activated to release inflammatory mediators that activate downstream NLRP3 inflammasome to release IL-1β and IL-18. These cytokines activate inflammatory M1 macrophages to induce the differentiation of osteoclast precursor cell into osteoclasts. The osteoclast then binds to bone resulting in bone resorption, osteolysis, and implant failure. NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; RANK, regulated by receptor activator of nuclear factor-κB; c-Fms, receptor for colony stimulating factor-1.
Figure 2:
Figure 2:
Activation of Complement system by titanium metal particles in Implant failure. The titanium metal debris activates C3 convertase (C4b2a) to cleave C3 into C3a and C3b. The resulting C3b binds to C3 convertase to become C5 convertase (C4b2a3b) which then cleaves C5 into C5a and C5b. C3a and C5a act as anaphylatoxins to induce an inflammatory response. C5b binds to other complement fragments starting with the binding to C6 to form C5b6 complex which then binds to C7 and C8 in a sequential manner. The C5bC7C8 complex binds to multiple molecules of C9 to form a membrane attack complex (C5b-9 complex). The complement fragments and membrane attack complex bind to the surface of the titanium implant resulting in the degradation of the implant and thus leading to implant failure.

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