Establishing clinically meaningful ranges of metal hypersensitivity in orthopaedic patients using COVID-19 vaccine-induced adaptive immune responses from fully vaccinated adults.

Background: This study aimed to assess metal sensitization ranges among orthopaedic patients by comparing adaptive immune responses in all-comer pre- and post-operative orthopaedic adults who were COVID-19 unvaccinated or vaccinated vs patients with a painful aseptic implant by lymphocyte transformation test (LTT) to SARS-CoV-2-Spike-Protein (SP) and implant metal(s), respectively.

Methods: Data were retrospectively reviewed from three independent groups: unvaccinated COVID-19 adults (n = 23); fully COVID-19 vaccinated adults (n = 35); unvaccinated, painful aseptic implant patients with history of metal allergy (n = 98). Standard in vitro LTT for SP and implant metal(s) (nickel, cobalt) were performed and rated as negative (stimulation index [SI]<2), mild (SI ≥ 2), positive (SI ≥ 4-15), and high sensitization (SI > 15) adaptive immune responses to tested antigen.

Translational Characterization of Macrophage Responses to Stable and Non-Stable CoCrMo Wear and Corrosion Debris Generated In-Situ for Total Hip Replacement.

Metal wear and corrosion debris remain a limiting factor for long-term durability of total hip replacement (THR). Common wear particle production techniques for research differ from the actual tribocorrosion processes at the implant site, potentially causing loss of valuable information. The aim of this study was to investigate reactions to freshly generated and time-stabilized particles and ions released from CoCrMo-alloy using a bio-tribometer, which mimics conditions of the periprosthetic environment.

Metal-induced delayed type hypersensitivity responses potentiate particle induced osteolysis in a sex and age dependent manner.

It is widely recognized that innate macrophage immune reactions to implant debris are central to the inflammatory responses that drive biologic implant failure over the long term. Less common, adaptive lymphocyte immune reactions to implant debris, such as delayed type hypersensitivity (DTH), can also affect implant performance. It is unknown which key patient factors, if any, mediate these adaptive immune responses that potentiate particle/macrophage mediated osteolysis.

Particulate Debris Released From Breast Implant Surfaces Is Highly Dependent on Implant Type.

Background: Although breast implants (BIs) have never been safer, factors such as implant debris may influence complications such as chronic inflammation and illness such as ALCL (anaplastic large cell lymphoma). Do different types of BIs produce differential particulate debris?

Objectives: The aim of this study was to quantify, investigate, and characterize the size, amount, and material type of both loosely bound and adherent surface particles on 5 different surface types of commercial BIs.

Methods: Surface particles from BIs of 5 surface types (n = 5/group), Biocell, Microcell, Siltex, Smooth, SmoothSilk, and Traditional-Smooth, were: (1) removed by a rinsing procedure and (2) removed with ultrapure adhesive carbon tabs.

Do Battlefield Injury-acquired Indwelling Metal Fragments Induce Metal Immunogenicity?

Background: A battlefield-related injury results in increased local and systemic innate immune inflammatory responses, resulting in wound-specific complications and an increased incidence of osteoarthritis. However, little is known about whether severe injuries affect long-term systemic homeostasis, for example, immune function. Moreover, it also remains unknown whether battlefield-acquired metal fragments retained over the long term result in residual systemic effects such as altered immune reactivity to metals.

The Inflammatory Effects of Breast Implant Particulate Shedding: Comparison With Orthopedic Implants.

Currently, there is a dearth of information regarding the degree of particle shedding from breast implants (BIs) and what are the general biological consequences of BI debris. Thus, it is unclear to what degree BI debris compromises the long-term biological performance of BIs. For orthopedic implants, it is well established that the severity of biological reactivity to implant debris governs long-term clinical performance.

Transition from metal-DTH resistance to susceptibility is facilitated by NLRP3 inflammasome signaling induced Th17 reactivity: Implications for orthopedic implants.

Metal hypersensitivity has been recognized as an adverse biologic reaction that can compromise total joint arthroplasty (TJA) performance. However, the etiology of metal hypersensitivity responses in TJAs remains unclear. Metal implant debris is known to act as a danger signal that drives NLRP3 inflammasome activation.

CoCrMo alloy . UHMWPE Particulate Implant Debris Induces Sex Dependent Aseptic Osteolysis Responses using a Murine Model.

Background: The rate of revision for some designs of total hip replacements due to idiopathic aseptic loosening has been reported as higher for women. However, whether this is environmental or inherently sex-related is not clear.

Objective: Can particle induced osteolysis be sex dependent? And if so, is this dependent on the type of implant debris (.

Cobalt Alloy Implant Debris Induces Inflammation and Bone Loss Primarily through Danger Signaling, Not TLR4 Activation: Implications for DAMP-ening Implant Related Inflammation.

Cobalt alloy debris has been implicated as causative in the early failure of some designs of current total joint implants. The ability of implant debris to cause excessive inflammation via danger signaling (NLRP3 inflammasome) vs. pathogen associated pattern recognition receptors (e.

TLR4 (not TLR2) dominate cognate TLR activity associated with CoCrMo implant particles.

Innate immune reactions to orthopedic implant debris are the primary cause of total joint replacement (TJR) failure over the long term (15-20 years). The role of pathogen associated pattern recognition receptors (i.e.

Implant debris particle size affects serum protein adsorption which may contribute to particle size-based bioreactivity differences.

Biologic reactivity to orthopedic implant debris mediates long-term clinical performance of total joint arthroplasty implants. However, the reasons that some facets of implant debris (e.g.

Osteoclasts lose innate inflammatory reactivity to metal and polymer implant debris compared to monocytes/macrophages.

Long-term aseptic failures of joint replacements are generally attributed to implant debris-induced inflammation and osteolysis. This response is largely mediated by immune and bone cells (monocytes/macrophages and osteoclasts, respectively), that in the presence of implant debris (e.g.

Cobalt-alloy implant debris induce HIF-1α hypoxia associated responses: a mechanism for metal-specific orthopedic implant failure.

The historical success of orthopedic implants has been recently tempered by unexpected pathologies and early failures of some types of Cobalt-Chromium-Molybdenum alloy containing artificial hip implants. Hypoxia-associated responses to Cobalt-alloy metal debris were suspected as mediating this untoward reactivity at least in part. Hypoxia Inducible Factor-1α is a major transcription factor involved in hypoxia, and is a potent coping mechanism for cells to rapidly respond to changing metabolic demands.

Increasing both CoCrMo-alloy particle size and surface irregularity induces increased macrophage inflammasome activation in vitro potentially through lysosomal destabilization mechanisms.

Recent investigations indicate that innate immune "danger-signaling" pathways mediate metal implant debris induced-inflammatory responses, for example, NALP3 inflammasome. How the physical characteristics of particles (size, shape, and chemical composition) affect this inflammatory reactivity remains controversial. We examined the role of Cobalt-Chromium-Molybdenum (CoCrMo) alloy particle shape and size on human macrophage phagocytosis, lysosomal destabilization, and inflammasome activation.