Biologic Responses to Orthopedic Implants

Innate and Adaptive Immune Responses to Implant Debris

Abstract

Almost 20% of joint replacement implants fail at 15 to 20 years.¹ Reports suggest that systemic effects of metal-on-metal implants and local effects of total joint arthroplasty implants contributing to implant failure are immune system based.² Sometimes implant wear debris can cause implant failure resulting from bone fracture, infection, or implant fracture/failure; most often, aseptic osteolysis or loosening leads to wear debris. Debris is produced by wear (primary) or by corrosion. Corrosion—chemical oxidation comprising reduction reactions involving electron transport—produces electrochemical degradation. Metallic implant degradation occurs when electrochemical dissolution and mechanical/physical wear are combined (i.e., tribocorrosion).^3,4 With metal-on-metal implants, even with relatively low levels of wear and particle release, pathology caused by metal debris such as pseudotumor/fibrous tissue growth can lead to early implant failure.

The immune system responds to implant debris by forming myeloid progenitor cells and lymphoid stem cells—responsible for innate (nonspecific) and adaptive (specific) immune reactivity, respectively. Innate immunity is controlled by macrophages, is antigen independent, elicits an immediate maximal response, is not antigen specific, and results in no (little) immunologic memory after exposure (Figure 1). In contrast, adaptive immunity is controlled by lymphocytes, is antigen dependent, involves lag time between exposure and maximal response, is antigen specific, and results in immunologic memory after exposure. Granuloma gradually invades the implant/bone interface, causing pain and implant loosening.

Figure 1: Traditional aspects of innate immunology.

New implants designed to minimize debris reflect these rules: (A) more implant debris → increased inflammation; (B) increased particle load → increased inflammation; and (C) larger particles → increased inflammation. Sparse implant debris leads to greater inflammatory response because the concentration of phagocytosable particles reflects both particle size and volume, and equal numbers of particles of different sizes can elicit different responses. Another rule states that (D) reactivity to metals > reactivity to polymers.

Models of implant-induced osteolysis show a central role for macrophages and suggest that the inflammatory pathway is critical for pharmacologic management of implant debris problems (SDC Figure 1, https://links.lww.com/BRS/B92). Hypersensitivity allows lymphocytes to become activated during implant corrosion and wear and is diagnosed by dermal patch testing and by lymphocyte transformation testing; the latter testing yields quantitative (clear) and objective results, and assesses the clinical impact of challenge agents such as ions and particles. Most often, aseptic implant failure over time is due to slow subtle innate macrophage reactivity to particulate debris, but in some cases, adaptive immune response (excessive response to relatively little debris) causes early failure (SDC Figure 2, https://links.lww.com/BRS/B117). Identifying individuals who are susceptible to specific types of inflammation may reduce risk while helping to avoid untoward immune reactivity.