Ceramic orthopaedic implants are increasingly popular due to the need for robust total joint replacement implants that have a high success rate long-term and do not induce biological responses in patients. This study was designed to investigate the biological effects of ceramic nanopowders containing aluminium oxide or zirconium oxide to activate the human macrophage THP-1 cell line. In vitro investigation of pro-inflammatory gene expression and chemokine secretion was performed studied using RT-qPCR and ELISA, respectively. TLR4 inhibition, using a small-molecule inhibitor, was used to determine whether ceramic-mediated inflammation occurs in a similar manner to that of metals such as cobalt. THP-1 macrophages were primed with ceramics or LPS and then treated with ATP or ceramics, respectively, to determine whether these nanopowders are involved in the priming or activation of the NLRP3 inflammasome through IL-1β secretion. Cells treated with ceramics significantly increased pro-inflammatory gene expression and protein secretion which was attenuated through TLR4 blockade. Addition of ATP to cells following ceramic treatment significantly increased IL-1β secretion. Therefore, we identify the ability of ceramic metal oxides to cause a pro-inflammatory phenotype in THP-1 macrophages and propose the mechanism by which this occurs is primarily via the TLR4 pathway which contributes to inflammasome signalling.
Osteoarthritis (OA) is a metabolically active condition characterised by loss of protective hyaline cartilage on joint surfaces. The subsequent contact of articulating bone surfaces within joints leads to subchondral sclerosis, cyst formation as well as osteophytes. This manifests clinically as joint pain, stiffness, swelling and loss of function for 10% of men and 18% of women aged over 60 years [1]. There are no licenced medications to limit OA progression and when symptoms are refractory to conservative treatments such as analgesia and physiotherapy, total joint arthroplasty (TJA) is indicated. Total joint replacementTJA is an effective treatment in end-stage OA using biomaterials to replace diseased joint surfaces and in 2019 there were 95,677 primary total hip replacements performed in England, Wales and Northern Ireland with osteoarthritis being indicated in 91.5% of cases[2]. This number is set to increase with our ageing population and rising obesity. As implants last on average for 78.9% at 20 years there is an urgent need to understand mechanisms driving implant failure, as revision surgery is associated with increased morbidity, mortality, venous thromboembolism rates and poorer subsequent function [3].The most common combination of hip replacement bearing surfaces are a metal alloy femoral head component articulating with a polyethylene acetabular cup, which has been in use since the development of the primary total hip replacement by Sir John Charnley in the 1960s [4]. However, metal-onpolyethylene (MoP) implants have been implicated in adverse reactions to debris as a result of phagocytosis of particulate debris by peri-implant macrophages, leading to osteolysis [5]. Ceramics have become increasingly popular as an alternative bearing surface in femoral head components as compared to MoP, as they are considered to be more biologically inert and have high wear resistance rates, in addition to reduced metal ion release from taper corrosion, which is observed in metal implants complicated by aseptic, lymphocyte-dominated vasculitis lesion (ALVAL)(6, 7). Given the increasing proportion of use of ceramic-on-polyethylene (CoP)
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