Plastic response of macrophages to metal ions and nanoparticles in time mimicking metal implant body environment.

The paradigm of using metal biomaterials could be viewed from two sides - treatment of wide spectrum of degenerative diseases, and debris release from materials. After implant insertion, metal nanoparticles (NPs) and ions are released not only upon the first contact with cells/tissues, but in continual manner, which is immediately recognized by immune cells. In this work, the effects of metal nanoparticles (TiO2, Ni) and ions (Ni2+, Co2+, Cr3+, Mo6+) on primary human M0 macrophages from the blood samples of osteoarthritic patients undergoing total arthroplasty were studied in order to monitor immunomodulatory effects on the cells in a real-time format. The highest NiNPs concentration of 10 µg/ml had no effect on any of macrophage parameters, while the Ni2+ ions cytotoxicity limit for the cells is 0.5 mM. The cytotoxic effects of higher Ni2+ concentration revealed mitochondrial network fragmentation leading to mitochondrial dysfunction, accompanied by increased lysosomal activity and changes in pro-apoptotic markers. The suppression of M2 cell formation ability was connected to presence of Ni2+ ions (0.5 mM) and TiO2NPs (10 µg/ml). The immunomodulatory effect of Mo6+ ions, controversially, inhibit the formation of the cells with M1 phenotype and potentiate the thread-like shape M2s with increased chaotic cell movement. To summarize, metal toxicity depends on the debris form. Both, metal ions and nanoparticles affect macrophage size, morphological and functional parameters, but the effect of ions is more complex and likely more harmful, which has potential impact on healing and determines post-implantation reactions.

Cytotoxic effects and comparative analysis of Ni ion uptake by osteoarthritic and physiological osteoblasts.

Nickel(Ni)-containing materials have been widely used in a wide range of medical applications, including orthopaedics. Despite their excellent properties, there is still a problem with the release of nickel ions into the patient's body, which can cause changes in the behaviour of surrounding cells and tissues. This study aims to evaluate the effects of Ni on bone cells with an emphasis on the determination of Ni localization in cellular compartments in time. For these purposes, one of the most suitable models for studying the effects induced by metal implants was used-the patient's osteoarthritic cells. Thanks to this it was possible to simulate the pathophysiological conditions in the patient's body, as well as to evaluate the response of the cells which come into direct contact with the material after the implantation of the joint replacement. The largest differences in cell viability, proliferation and cell cycle changes occurred between Ni 0.5 mM and 1 mM concentrations. Time-dependent localization of Ni in cells showed that there is a continuous transport of Ni ions between the nucleus and the cytoplasm, as well as between the cell and the environment. Moreover, osteoarthritic osteoblasts showed faster changes in concentration and ability to accumulate more Ni, especially in the nucleus, than physiological osteoblasts. The differences in Ni accumulation process explains the higher sensitivity of patient osteoblasts to Ni and may be crucial in further studies of implant-derived cytotoxic effects.

Mechanical complications and infection control comparison of custom-made and prefabricated articular hip spacers in the treatment of periprosthetic infection.

OBJECTIVES: The purpose of our study was to compare the complication rate and the outcomes of custom-made spacers (C-spacers) and prefabricated articular spacers (P-spacers) in the treatment of periprosthetic infection. PATIENTS AND METHODS: In this retrospective study, 78 patients (44 females, 34 males; mean age: 68.5±9.48 years; range, 47 to 82 years) with articular spacers implanted in our institution were analyzed between January 2009 and December 2019. We recorded implant results as per mechanical complications, infection control, the interval from surgery to definitive hip replacement, and the rate of achieving recovery of joint function after stage two arthroplasty. RESULTS: There were 29 revised spacers; 18 of them were C-spacers and 11 were P-spacers (p=0.0383). A total of 16 dislocations were recorded, of which six were dislocations of C-spacers, and 10 were dislocations of P-spacers (p=0.0082). Additionally, we registered four spacer breakages, all of which occurred in C-spacers (p=0.295). C-spacers failed early, at an mean interval of 2.2 weeks after implantation, and P-spacers failed later, with an mean of 9.3 weeks after implantation (p=0.0187). A total of nine reinfection complications of spacers were registered; only one infection of P-spacers, and eight infections related to C-spacers (p=0.2583). Definitive revision total hip arthroplasty (rTHA) after spacer explantation and successful treatment of the infection occurred in 63 cases out of 78 patients. Definitive rTHA occurred after the use of C-spacers in 41 (78%) patients and after the use of C-spacers in 22 (84%) patients (p=0.7816). C-spacers had a mean interval from spacer implantation to definitive rTHA of 6.56±6.03 months, and P-spacers had a mean interval of 4±1.93 months (p=0.0164). CONCLUSION: Custom-made spacers were shown to have lower mechanical complication rates than prefabricated ones but more infection complications. Prefabricated spacers had more dislocations and fewer breakages. Custom-made spacer mechanical failures occurred earlier compared to prefabricated ones.