Background Early adverse tissue reactions around metalon-metal (MoM) hip replacements, especially pseudotumors, are a major concern. Because the causes and pathomechanisms of these pseudotumors remain largely unknown, clinical monitoring of patients with MoM bearings is challenging. Questions/purposes The purpose of this study was to compare the lymphocyte subpopulations in peripheral blood from patients with a failed MoM hip implant with and without a pseudotumor and patients with a well-functioning MoM hip implant without a pseudotumor. Potential differences in the systemic immune response are expected to reflect local differences in the periprosthetic tissues. Methods Consenting patients who underwent a revision of a failed MoM hip implant at The Ottawa Hospital (TOH) from 2011 to 2014, or presented with a well-functioning MoM hip implant for a postoperative clinical followup at TOH from 2012 to 2013, were recruited for this study, unless they met any of the exclusion criteria (including diagnosed conditions that can affect peripheral blood lymphocyte subpopulations). Patients with a failed implant were divided into two groups: those with a pseudotumor (two hip resurfacings and five total hip arthroplasties

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Previous studies using nonlinear microscopy have demonstrated that osteoarthritis (OA) is characterized by the gradual replacement of Type II collagen with Type I collagen. The objective of this study was to develop a prototype nonlinear laser scanning microendoscope capable of resolving the structural differences of collagen in various orthopaedically relevant cartilaginous surfaces. The current prototype developed a miniaturized femtosecond laser scanning instrument, mounted on an articulated positioning system, capable of both conventional arthroscopy and second-harmonic laser-scanning microscopy. Its optical system includes a multi-resolution optical system using a gradient index objective lens and a customized multi-purpose fiber optic sheath to maximize the collection of backscattered photons or provide joint capsule illumination. The stability and suitability of the prototype arthroscope to approach and image cartilage were evaluated through preliminary testing on fresh, minimally processed, and partially intact porcine knee joints. Image quality was sufficient to distinguish between hyaline cartilage and fibrocartilage through unique Type I and Type II collagen-specific characteristics. Imaging the meniscus revealed that the system was able to visualize differences in the collagen arrangement between the superficial and lamellar layers. Such detailed in vivo imaging of the cartilage surfaces could obviate the need to perform biopsies for ex vivo histological analysis in the future, and provide an alternative to conventional external imaging to characterize and diagnose progressive and degenerative cartilage diseases such as OA. Moreover, this system is readily customizable and may provide a suitable and modular platform for developing additional tools utilizing femtosecond lasers for tissue cutting within the familiar confines of two or three portal arthroscopy techniques.

A T cell-mediated hypersensitivity reaction has been reported in some patients with CoCrMo-based implants. However, the role of cobalt and chromium ions in this reaction remains unclear. The objective of the present study was to analyze the effects of Co and Cr in culture medium, as well as the effects of culture supernatants of macrophages exposed to Co or Cr , on the migration of lymphocytes. The release of cytokines/chemokines by macrophages exposed to Co and Cr was also analyzed. The migration of murine lymphocytes was quantified using the Boyden chamber assay and flow cytometry, while cytokine/chemokine release by J774A.1 macrophages was measured by ELISA. Results showed an ion concentration-dependent increase in TNF-α and MIP-1α release and a decrease in MCP-1 and RANTES release. Migration analysis showed that the presence of Co (8 ppm) and Cr (100 ppm) in culture medium increased the migration of T lymphocytes, while it had little or no effect on the migration of B lymphocytes, suggesting that Co and Cr can stimulate the migration of T but not B lymphocytes. Levels of T lymphocyte migration in culture medium containing Co or Cr were not statistically different from those in culture supernatants of macrophages exposed to Co or Cr , suggesting that the effects of the ions and chemokines were not additive, possibly because of ion interference with the chemokines and/or their cognate receptors. Overall, results suggest that Co and Cr are capable of stimulating the migration of T (but not B) lymphocytes in the absence of cytokines/chemokines, and could thereby contribute to the accumulation of more T than B lymphocytes in periprosthetic tissues of some patients with CoCrMo-based implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:916-924, 2017.

Adverse tissue reactions to metal implants, including pseudotumors, can compromise implant functionality and survivorship. The identification of specific proteins in the synovial fluid (SF) of hip arthroplasty patients with a pseudotumor may lead to a better understanding of the underlying pathomechanisms. The objective of the present study was to compare the protein content of SF from patients with a short-term metal-on-metal hip implant associated with a pseudotumor and patients with a long-term metal-on-polyethylene hip implant associated with periprosthetic osteolysis. Discovery proteomics was used to identify differentially abundant proteins in albumin-depleted SF. In toto, 452 distinct proteins (present in at least half of the patients in one or both groups) were identified. Thirty of these 452 proteins were differentially abundant between the two groups, including two potential biomarkers: 6-phosphogluconate dehydrogenase (which plays a major protective role against oxidative stress) for the pseudotumor group, and scavenger receptor cysteine-rich type 1 protein M130 (which is involved in low-grade inflammation) for the periprosthetic osteolysis group. Other differentially abundant proteins identified suggest the presence of an adaptive immune response (particularly a type-IV hypersensitivity reaction), necrosis, and greater oxidative stress in patients with a pseudotumor. They also suggest the presence of an innate immune response, oxidative stress, tissue remodeling, and apoptosis in both patient groups, although differences in the specific proteins identified in each group point to differences in the pathomechanisms. Overall, results provide insights into the molecular mechanisms underlying metal-related pseudotumors and periprosthetic osteolysis, and may ultimately help elucidate pseudotumor etiology and assess the risk that asymptomatic pseudotumors will develop into an aggressive lesion. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1849-1859, 2018.