Novel Nanoparticulate and Ionic Titanium Antigens for Hypersensitivity Testing

Titanium is used in a wide variety of materials ranging from medical devices to materials used in everyday life. Adverse biological reactions that could occur in patients, consumers, and workers should be monitored and prevented. There is a lack of available agents to test and predict titanium-related hypersensitivity. The aim of this study was to develop two bioavailable titanium substances in ionic and nanoparticulate form to serve as antigens for hypersensitivity testing in vitro. Peripheral blood mononuclear cells from 20 test subjects were stimulated with the antigens and secretion of monocytic and lymphatic cytokines and chemokines were measured by a multiplex bead assay. Lymphocyte stimulation indices were also determined in a subset of test subjects by measuring CD69 and HLA-DR expression by flow cytometry. Cytokine profiling revealed that both antigens increased production of typical monocyte and macrophage secreted cytokines after 24 h, with significant increases in IL-1β, IL-7, IL-10, IL-12, IL-2R, IL-6, GM-CSF, TNF-α, IL-1RA, MIP-1α, MIP-1β, IFN-α, and IL-15. Lymphatic cytokines and chemokines were not significantly induced by activation. After seven days of stimulation, ionic-Ti (2.5 μg/mL) caused proliferation (stimulation index > 2) of CD4+ cells and CD8+ cells in all persons tested (N = 6), while titanium dioxide nanoparticles (50 μg/mL) only caused significant proliferation of CD4+ cells. Our preliminary results show that the experimental titanium antigens, especially the ionic form, induce a general inflammatory response in vitro. A relevant cohort of test subjects is required to further elucidate their potential for predictive hypersensitivity testing.publishedVersio

Strength of side-to-side and step-cut repairs in tendon transfers: biomechanical testing of porcine flexor tendons

The aim of the study was to compare side-to-side with step-cut repairs to determine how much of the width it is possible to remove and still keep the repair strong enough to start active mobilization. Porcine flexor tendons were used to create side-to-side, one-third step-cut and half step-cut repairs. There were 15 repairs in each group. The tensile properties of the constructs were measured in a biomechanical testing machine. All repairs failed by the sutures splitting the tendon longitudinally. The maximum load and stiffness were highest in the side-to-side group. Our findings suggest that the half step-cut repair can withstand the forces exerted during active unrestricted movement of the digits in tendons of this size. The advantage of the step-cut repair is reduced bulkiness and less friction, which might compensate for the difference in strength.acceptedVersio

Label-free monitoring of uptake and toxicity of endoprosthetic wear particles in human cell cultures

The evaluation of the biological effects of endoprosthetic wear particles on cells in vitro relies on a variety of test assays. However, most of these methods are susceptible to particle-induced interferences; therefore, label-free testing approaches emerge as more reliable alternatives. In this study, impedance-based real-time monitoring of cellular viability and metabolic activity were performed following exposure to metallic and ceramic wear particles. Moreover, label-free imaging of particle-exposed cells was done by high-resolution darkfield microscopy (HR-ODM) and field emission scanning electron microscopy (FESEM). The isolated human fibroblasts were exposed to CoCr28Mo6 and alumina matrix composite (AMC) ceramic particles. HR-ODM and FESEM revealed ingested particles. For impedance measurements, cells were seeded on gold-plated microelectrodes. Cellular behavior was monitored over a period of 48 h. CoCr28Mo6 and AMC particle exposure affected cell viability in a concentration-dependent manner, i.e., 0.01 mg/mL particle solutions led to small changes in cell viability, while 0.05 mg/mL resulted in a significant reduction of viability. The effects were more pronounced after exposure to CoCr28Mo6 particles. The results were in line with light and darkfield microcopy observations indicating that the chosen methods are valuable tools to assess cytotoxicity and cellular behavior following exposure to endoprosthetic wear particles.publishedVersio

Cementing techniques for total knee arthroplasty in Norwegian hospitals; a questionnaire-based study

Background - Cementing technique in total knee arthroplasty (TKA) may influence implant survival. There is limited knowledge about the results with clinically used techniques. The aim of this study was to investigate cementing techniques for TKA in Norwegian hospitals, to compare widely used techniques to recommendations from the literature, and to investigate variation within hospitals. Methods - A questionnaire requesting information about cementing techniques were distributed to all Norwegian orthopedic surgeons performing TKAs regularly in 2020. Data was analyzed using descriptive statistical methods. Results - We acquired 121 responses out of 257 surgeons. They were from 45 out of 56 hospitals, and at least half of the TKA surgeons from 20 hospitals, constituting 79 surgeons. All responders used pulsatile lavage. Cement application to both the tibial plateau and stem (full cementation) was practiced by 61%. Application of cement to both implant and bone was done by 70% of surgeons. Techniques to improve cement penetration were used by 86%. Only 35% of surgeons aimed to get a cement mantle thickness between 3–5 mm. Flexing the knee joint to remove excess cement was done by 82%. We found that in 55% of 20 hospitals the surgeons did not agree on the use of common guidelines in their ward. Conclusions - The majority of the responders used recommended techniques from the literature when cementing TKA. At more than half of the eligible hospitals, surgeons disagreed about their hospitals’ use of common guidelines. Focusing on developing evidence-based guidelines would be beneficial for TKA-quality

Inflammatory tissue reactions around aseptically loose cemented hip prostheses: A retrieval study of the Spectron EF stem with Reflection All-Poly acetabular cup

The cemented Spectron EF stem in combination with the cemented non-crosslinked Reflection All-Poly cup showed a high rate of mid-term aseptic loosening. However, the failure mechanisms are not fully known. We assessed the inflammatory tissue reactions and wear particles in periprosthetic tissues, implant wear and blood metal ion levels in 28 patients with failed implants. Histological analysis showed a macrophage pre-dominant pattern with randomly distributed lymphocytes, with various amounts of neutrophils and giant cells. The number of different cell types in the tissue samples from patients in the cup group and in the stem group was similar. Wear particles, mainly ZrO2, CoCrMo, and polyethylene particles of different sizes and shapes, were associated with macrophages/giant cells, and total particle load/mm2 was higher in cases of stem loosening. The Spectron EF stems were heavily worn, abraded, and polished. Stem abrasion correlated with metal ion concentrations in blood. The median polyethylene wear rate of the Reflection cups was 0.23 mm/year. The high proximal roughness of the Spectron EF stem resulted in excessive cement wear during loosening. The resulting inflammatory tissue responses to the degradation products both from the cup and the stem led to massive osteolysis and subsequent implant loosening.publishedVersio

Polycrystalline Diamond Coating on Orthopedic Implants: Realization and Role of Surface Topology and Chemistry in Adsorption of Proteins and Cell Proliferation

Polycrystalline diamond has the potential to improve the osseointegration of orthopedic implants compared to conventional materials such as titanium. However, despite the excellent biocompatibility and superior mechanical properties, the major challenge of using diamond for implants, such as those used for hip arthroplasty, is the limitation of microwave plasma chemical vapor deposition (CVD) techniques to synthesize diamond on complex-shaped objects. Here, for the first time, we demonstrate diamond growth on titanium acetabular shells using the surface wave plasma CVD method. Polycrystalline diamond coatings were synthesized at low temperatures (∼400 °C) on three types of acetabular shells with different surface structures and porosities. We achieved the growth of diamond on highly porous surfaces designed to mimic the structure of the trabecular bone and improve osseointegration. Biocompatibility was investigated on nanocrystalline diamond (NCD) and ultrananocrystalline diamond (UNCD) coatings terminated either with hydrogen or oxygen. To understand the role of diamond surface topology and chemistry in the attachment and proliferation of mammalian cells, we investigated the adsorption of extracellular matrix proteins and monitored the metabolic activity of fibroblasts, osteoblasts, and bone-marrow-derived mesenchymal stem cells (MSCs). The interaction of bovine serum albumin and type I collagen with the diamond surfaces was investigated by confocal fluorescence lifetime imaging microscopy (FLIM). We found that the proliferation of osteogenic cells was better on hydrogen-terminated UNCD than on the oxygen-terminated counterpart. These findings correlated with the behavior of collagen on diamond substrates observed by FLIM. Hydrogen-terminated UNCD provided better adhesion and proliferation of osteogenic cells, compared to titanium, while the growth of fibroblasts was poorest on hydrogen-terminated NCD and MSCs behaved similarly on all tested surfaces. These results open new opportunities for application of diamond coatings on orthopedic implants to further improve bone fixation and osseointegration.publishedVersio

Tribology of Medical Devices

Importance of tribology in a number of medical devices and surgical instruments is reviewed, including artificial joints, artificial teeth, dental implants and orthodontic appliances, cardiovascular devices, contact lenses, artificial limbs and surgical instruments. The current focus and future developments of these medical devices are highlighted from a tribological point of view, together with the underlying mechanisms

The effect of blood protein adsorption on cellular uptake of anatase TiO2 nanoparticles

Protein adsorption onto nanoparticles (NPs) in biological fluids has emerged as an important factor when testing biological responses to NPs, as this may influence both uptake and subsequent toxicity. The aim of the present study was to quantify the adsorption of proteins onto TiO2 NPs and to test the influence on cellular uptake. The surface composition of the particles was characterized by thermal analysis and by X-ray photoelectron spectroscopy. The adsorption of three blood proteins, ie, human serum albumin (HSA), γ-globulins (Glbs), and fibrinogen (Fib), onto three types of anatase NPs of different sizes was quantified for each protein. The concentration of the adsorbed protein was measured by ultraviolet-visible spectrophotometry using the Bradford method. The degree of cellular uptake was quantified by inductivity coupled plasma mass spectroscopy, and visualized by an ultra-high resolution imaging system. The proteins were adsorbed onto all of the anatase NPs. The quantity adsorbed increased with time and was higher for the smaller particles. Fib and Glbs showed the highest affinity to TiO2 NPs, while the lowest was seen for HSA. The adsorption of proteins affected the surface charge and the hydrodynamic diameter of the NPs in cell culture medium. The degree of particle uptake was highest in protein-free medium and in the presence HSA, followed by culture medium supplemented with Glbs, and lowest in the presence of Fib. The results indicate that the uptake of anatase NPs by fibroblasts is influenced by the identity of the adsorbed protein