Aims. Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs. Patients and Methods. We investigated tissue collected at revision surgery from nine ceramic-on-ceramic articulations. we compared our findings with tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes. The latter were analyzed to assess the amount of tissue fibrosis that might have been present at the time of implantation to enable evaluation, in relation to implantation time, of any subsequent response in the tissues. Results. There was a significant increase in tissue fibrosis with implantation time for all implant types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was significantly increased compared with metal-on-metal and ceramic-on-polyethylene. Additionally, we found ceramic wear particles in the periprosthetic tissue of ceramic implants. Fibroblasts responded with expression of cytokines when cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA) ceramic surfaces. This response was more pronounced on ATZ ceramics compared with ZTA ceramics. The same inflammatory response was observed with peripheral blood mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion. Our findings therefore, corroborate the previous findings that ceramic-on-ceramic periprosthetic revision tissue is fibrous and offer an explanation for this observation. We detected a long-term inflammatory response of PBMCs and an inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings partially explain the fibrotic tissue change in periprosthetic tissue of ceramic-on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882–90

Introduction. There are several potential biological mechanisms that may influence aseptic implant failure including excessive innate and adaptive immune responses to implant debris. We investigated the hypothesis that patients with painful total joint replacements will exhibit elevated levels of metal reactivity and inflammatory markers compared to patients with well-performing TJA. We evaluated this hypothesis by testing for metal hypersensitivity using in vitro LTT assay and analyzing serum levels of selected inflammatory markers. Methods. Subject Groups: Blinded de-identified data from patients with TJR referred for metal hypersensitivity testing using a lymphocyte transformation test (LTT) and serum markers of inflammation using Luminex Multi-Analyte Assay was approved by Rush University IRB and retrospectively reviewed. None of the patients had radiographically identifiable osteolysis. Two groups of TJA patients were tested: Group 1: Well-functioning implant (<3 yrs. post-op), with no self-reported pain, i.e. <1 on 0–10 VAS scale (n=8) and Group 2: Painful TJR (<3 yrs. post-op), with self-determined pain of >8 on a 0–10 VAS scale at the time of blood draw (n=25). Metal-LTT: Peripheral blood mononuclear cells (PBMCs) were collected from 30mL of peripheral blood by Ficoll gradient separation. PBMCs were cultured with NiCl2. 3H Thymidine was added at day 5 of culture and 3H thymidine incorporation was analyzed using a beta scintillation counter at day 6. A stimulation index (SI) of reactivity was calculated by dividing scintillation counts per minute (cpms) of Ni challenged cells by those of untreated controls. A SI of <2 was considered nonreactive, 2 to <4 was mildly reactive and 4 to <8 was reactive. Luminex Assay: Serum samples were collected from whole blood and were analyzed according to manufacturer's protocols. Statistical analysis: Statistical differences were determined using unpaired t-test with Welch's correction with statistical significance at p≤0.1 (90% confidence interval). Results. To test if differences in metal sensitization exist among individuals with joint pain following TJR vs. well-functioning TJR (no pain), we analyzed each person-specific PBMC SI of reactivity to NiCl2. Painful TJR group exhibited greater sensitivity as demonstrated by significantly higher in vitro metal SI level. In general, inflammatory markers measured in serum among patients with pain following TJR were significantly increased compared to patients with no pain following TJR. Specifically, inflammatory markers that are classified as prototypical markers of a M1 inflammatory macrophage i.e. GMCSF, IL-12, IL-18, IL-1β and TNFα were significantly greater in TJR patients with pain compared to TJR patients with no pain. Due to this increase in inflammatory markers, IL-4, an anti-inflammatory marker was also significantly greater in TJR patients with pain in order to combat/mitigate the inflammatory microenvironment. While VEGF was the only marker that was significantly greater in TJR patients with no pain and is characteristic of M2 anti-inflammatory macrophage phenotype. Discussion. Metal sensitivity reactivity and serum markers of inflammation demonstrated significant differences between groups of patients with painful TJRs vs. well-functioning TJR. Classical markers of M1 phenotype were significantly greater in painful TJR group. Our data suggests that patients with self-reported pain following a TJR demonstrate active innate and adaptive immune responses that are significantly higher than patients with a well-performing TJR and that these differences are associated with detectable serum inflammatory markers. An important limitation of this study however, is that group subject numbers were low and that statistical differences found in these groups suggests these inflammatory markers may be more marked than was anticipated

Objectives

T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty.