The Immune Response to Implant Materials in Humans
ABSTRACT The etiology of aseptic loosening of prosthetic joint replacement components is unclear. Implant materials have been considered biologically inert, but recently studies indicate that inflammatory reactions directed against the implanted materials may contribute to aseptic loosening. Data suggesting a progression from a simple inflammatory reaction to complex immune responses against the biomaterials are reviewed. The cellular responses to particles of polymethylmethacrylate, ultrahigh molecular weight polyethylene, and alloys of cobalt-chromium and titanium were assayed in vitro to determine cell proliferation in patients with underlying diagnoses of osteoarthrosis, rheumatoid arthritis, and avascular necrosis who had joint replacement. Control populations were provided by patients with similar diagnoses who were preoperative surgical candidates. The underlying diagnoses did not seem to influence responses to particle stimulation. Elevated responses to both acrylic and cobalt-chromium were observed in patients with aseptically loosened prostheses. These findings suggest that the development of a cellular response to particulate debris may be significant in the pathogenesis of aseptic loosening.
- SourceAvailable from: Paul H Wooley
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- "Previous studies, including ours, indicate that peripheral monocytes from AL patients are activated and exhibit aggressive response to implant wear    . We have reported that the IL-1β production (mRNA and protein) in patients with stable implants are significantly lower (p b 0.025) than in AL patients . This finding was confirmed by an investigation in a large population of patients who were candidates for either primary TJR (n = 65) or revision surgery (n = 120) . "
ABSTRACT: There is currently no cure for aseptic loosening (AL) of total joint replacement (TJR) except surgical revision. The purpose of this study was to determine whether oral EM could improve the periprosthetic tissue profiles and reduce serum cytokine production in AL patients who are candidates for surgical revision. We recruited 32 AL patients. AL patients were treated with either EM (600 mg/day, n=18) or placebo (n=14) daily, started one month before surgery and ending on the day of surgery. Blood samples were obtained before EM treatment and during surgery. Periprosthetic tissues and joint fluids were collected during surgery. Our results demonstrate that oral EM reduces the inflammation of periprosthetic tissues, as manifested by the reduction of the numbers of infiltrating cells, CD68+ macrophages, RANKL+ cells, and TRAP+ cells. Remarkable decreases of TNFalpha (9.6-fold), IL-1beta (21.2-fold), and RANKL (76-fold) gene transcripts were observed in periprosthetic tissues of patients treated with oral EM. Serum levels of both TNFalpha and (to a lesser extent) IL-1beta were significantly reduced following EM treatment (p<0.05). Our results suggest that EM represents a biological cure or prevention for those patients who might need repeated revision surgeries and/or show the early signs of progressive osteolysis after TJR.Bone 04/2009; 44(4):671-7. DOI:10.1016/j.bone.2008.12.015 · 4.46 Impact Factor
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- "Based mostly on case reports, it has been suggested that hypersensitivity to Ti is associated with implant loosening (Wooley et al 1996; Matthew and Frame 1998), or skin reactions (Peters et al 1984; Yamauchi et al 2000; Tamai et al 2001; High et al 2006; Thomas et al 2006; Watanabe et al 2006). Diagnosis of contact allergy to metals usually relies on combination of anamnestic information and in vivo tests such as a epicutaneous patch test (Hallab et al 2001; Granchi et al 2006), and – in some instances – ex vivo tests such as a Lymphocyte Stimulation Test (LST) on cells from blood samples (Hallab et al 2001). "
ABSTRACT: Degradation products of titanium implants include free ions, organo-metallic complexes, and particles, ranging from nano to macro sizes. The biological effects, especially of nanoparticles, is yet unknown. The main objective of this study was to develop Ti-protein antigens in physiological solutions that can be used in testing of cellular responses. For this purpose, 0.1% TiO2 nanoparticles less than 100 nm were mixed with human serum albumin (HSA), 0.1% and 1%, in cell culture medium (DMEM, pH 7.2). The Ti concentrations in the resulting solutions were analyzed by inductively coupled plasma mass spectrometry. The stability of the nanoparticles in suspension was analyzed by UV-vis spectrophotometer and Dynamic Light Scattering. The concentration of Ti in suspension was dependent on the presence and concentration of HSA. Albumin prevented high aggregation rate of TiO2 nanoparticles in cell culture medium. It is shown that nano TiO2-protein stable aggregates can be produced under physiological conditions at high concentrations, and are candidates for use in cellular tests.International Journal of Nanomedicine 02/2008; 3(1):69-74. · 4.38 Impact Factor
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- "FDG-PET cannot distinguish the aseptically loosened from the infected joint replacement (Love et al., 2004). A significant number of cases of aseptic loosening are the result of an inflammatory/immune reaction (Wooley et al., 1996). Histopathological examinations of failed prostheses show that a synovial-like pseudomembranous structure develops. "
ABSTRACT: Despite significant advances in the understanding of its pathogenesis, infection remains a major cause of patient morbidity and mortality. While the presence of infection may be suggested by signs and symptoms, imaging tests are often used to localize or confirm its presence. There are two principal imaging test types: morphological and functional. Morphological tests include radiographs, computed tomography (CT), magnetic resonance imaging, and sonongraphy. These procedures detect anatomic, or structural, alterations produced by microbial invasion and host response. Functional imaging tests reflect the physiological changes that are part of this process. Prototypical functional tests are radionuclide procedures such as bone, gallium, labelled leukocyte and fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. In-line functional/morphological tomographic imaging systems, PET/CT and single photon emission tomography (SPECT)/CT, have revolutionized diagnostic imaging. These devices consist of a functional imaging device (PET or SPECT) joined together with a CT scanner. The patient undergoes both tests sequentially without leaving the examination table. Images from each study can be viewed separately and as fused images, providing precisely localized anatomic and functional information. It must be noted, however, that none of the current morphological or functional tests, either alone or in combination, are specific for infection and the goal of finding such an imaging test remains elusive.Cellular Microbiology 11/2007; 9(10):2323-33. DOI:10.1111/j.1462-5822.2007.01013.x · 4.82 Impact Factor