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The inflammatory response to wear particles derived from hip prothesis is considered a hallmark of periprosthetic osteolysis, which can ultimately lead to the need for revision surgery. Exosomes (Exos) have been associated with various bone pathologies, and there is increasing recognition in the literature that they actively transport molecules throughout the body. The role of wear particles in osteoblast-derived Exos is unknown, and the potential contribution of Exos to osteoimmune communication and periprosthetic osteolysis niche is still in its infancy. Given this, we investigate how titanium dioxide nanoparticles (TiO2 NPs), similar in size and composition to prosthetic wear particles, affect Exos biogenesis. Two osteoblastic cell models commonly used to study the response of osteoblasts to wear particles were selected as a proof of concept. The contribution of Exos to periprosthetic osteolysis was assessed by functional assays in which primary human macrophages were stimulated with bone-derived Exos. We demonstrated that TiO2 NPs enter multivesicular bodies, the nascent of Exos, altering osteoblast-derived Exos secretion and molecular cargo. No significant differences were observed in Exos morphology and size. However, functional assays reveal that Exos cargo enriched in uPA stimulates macrophages to a mixed M1 and M2 phenotype, inducing the release of pro- and anti-inflammatory signals characteristic of periprosthetic osteolysis. In addition, we demonstrated the expression of uPA in exosomes derived from the urine of patients with osteolysis. These results suggest that uPA can be a potential biomarker of osteolysis. In the future, uPa may serve as a possible non-invasive biomarker to identify patients at risk for peri-implant osteolysis.

Abstract Background The goal of this study is to propose a classification system with a common nomenclature for radiographic observations of periprosthetic bone changes following cTDR. Methods Aided by serial plain radiographs from recent cTDR cases (34 patients; 44 devices), a panel of experts assembled for the purpose of creating a classification system to aid in reproducibly and accurately identifying bony changes and assessing cTDR radiographic appearance. Subdividing the superior and inferior vertebral bodies into 3 equal sections, observed bone loss such as endplate rounding, cystic erosion adjacent to the endplate, and cystic erosion not adjacent to the endplate, is recorded. Determining if bone loss is progressive, based on serial radiographs, and estimating severity of bone loss (measured by the percentage of end plate involved) is recorded. Additional relevant bony changes and device observations include radiolucent lines, heterotopic ossification, vertebral body olisthesis, loss of core implant height, and presence of device migration, and subsidence. Results Serial radiographs from 19 patients (25 devices) implanted with a variety of cTDR designs were assessed by 6 investigators including clinicians and scientists experienced in cTDR or appendicular skeleton joint replacement. The overall agreement of assessments ranged from 49.9% (95% bootstrap confidence interval 45.1–73.1%) to 94.7% (95% CI 86.9–100.0%). There was reasonable agreement on the presence or absence of bone loss or radiolucencies (range: 58.4% (95% CI 51.5–82.7%) to 94.7% (95% CI 86.9–100.0%), as well as in the progression of radiolucent lines (82.9% (95% CI 74.4–96.5%)). Conclusions The novel classification system proposed demonstrated good concordance among experienced investigators in this field and represents a useful advancement for improving reporting in cTDR studies.

Background: Total disc replacement (TDR) is widely used in the treatment of cervical and lumbar spine pathologies. Although TDR infection, particularly delayed infection, is uncommon, the results can be devastating, and consensus on clinical management remains elusive. In this review of the literature, we asked: (1) What are the reported rates of TDR infection; (2) What are the clinical characteristics of TDR infection; and (3) How has infection been managed for TDR patients? Methods: We performed a search of the literature using PubMed and Embase to identify studies that reported TDR infection rates, the identification and management of TDR infection, or TDR failures with positive cultures. Twenty database studies (17 focusing on the cervical spine and 3 on the lumbar spine) and 10 case reports representing 15 patients were reviewed along with device Summary of Safety and Effectiveness Data reports. Results: We found a lack of clarity regarding how infection was diagnosed, indicating a variation in clinical approach and highlighting the need for a standard definition of TDR infection. Furthermore, while reported infection rates were low, the absence of a clear definition prevented robust data analysis and may contribute to underreporting in the literature. We found that treatment strategy and success rely on several factors including patient symptoms and time to onset, microorganism type, and implant positioning/stability. Conclusions: Although treatment strategies varied throughout the extant literature, common practices in eliminating infection and reconstructing the spine emerged. The results will inform future work on the creation of a more robust definition of TDR infection and as well as recommendations for management.

Abstract Background Recent studies indicate that, in addition to antibody production, lymphocyte responses to SARS-CoV-2 may play an important role in protective immunity to COVID-19 and a percentage of the general population may exhibit lymphocyte memory due to unknown/asymptomatic exposure to SARS-CoV-2 or cross-reactivity to other more common coronaviruses pre-vaccination. Total joint replacement (TJR) candidates returning to elective surgeries (median age 68 years) may exhibit similar lymphocyte and/or antibody protection to COVID-19 prior to vaccination Methods In this retrospective study, we analyzed antibody titters, lymphocyte memory, and inflammatory biomarkers specific for the Spike and Nucleocapsid proteins of the SARS-CoV-2 virus in a cohort of n=73 returning TJR candidates (knees and/or hips) pre-operatively. Results Peripheral blood serum of TJR candidate patients exhibited a positivity rate of 18.4% and 4% for IgG antibodies specific for SARS-CoV-2 nucleocapsid and spike proteins, respectively. 13.5% of TJR candidates exhibited positive lymphocyte reactivity (SI > 2) to the SARS-CoV-2 nucleocapsid protein and 38% to the spike protein. SARS-CoV-2 reactive lymphocytes exhibited a higher production of inflammatory biomarkers (i.e., IL-1β, IL-6, TNFα, and IL-1RA) compared to non-reactive lymphocytes. Conclusions A percentage of TJR candidates returning for elective surgeries exhibit pre-vaccination positive SARS-CoV-2 antibodies and T cell memory responses with associated pro-inflammatory biomarkers. This is an important parameter for understanding immunity, risk profiles, and may aid pre-operative planning. Trial registration Retrospectively registered.

Recognizing and adopting standardized terms for adverse local tissue reaction associated with tribocorrosion in total hip arthroplasty are essential for clear scientific discourse and clinical communication. Our goal was to develop terms that can be broadly applied to characterize the local tissue response to tribocorrosion debris, based on current evidence regarding the etiology of this failure mode and its consequences. The proposed standardized terms will improve the understanding and interpretation of analytical tests, advance diagnostic and treatment algorithms, and reduce confusion in research by maintaining consistent nomenclature.

All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15–25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or “aseptic loosening” is a potentially life-threatening condition due to the serious complications in older people (>75 yrs) of total joint replacement revision surgery. In some people implant debris (particles and ions from metals) can influence the adaptive immune system as well, giving rise to the concept of metal sensitivity. However, a consensus of studies agrees that the dominant form of this response is due to innate reactivity by macrophages to implant debris where both danger (DAMP) and pathogen (PAMP) signalling elicit cytokine-based inflammatory responses. This paper discusses implant debris induced release of the cytokines and chemokines due to activation of the innate (and the adaptive) immune system and the subsequent formation of osteolysis. Different mechanisms of implant-debris reactivity related to the innate immune system are detailed, for example, danger signalling (e.g., IL-1β, IL-18, IL-33, etc.), toll-like receptor activation (e.g., IL-6, TNF-α, etc.), apoptosis (e.g., caspases 3–9), bone catabolism (e.g., TRAP5b), and hypoxia responses (Hif1-α). Cytokine-based clinical and basic science studies are in progress to provide diagnosis and therapeutic intervention strategies.