Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophagesin vitro

González, Oscar C.; Smith, Robert L.; Goodman, Stuart B.

doi:10.1002/(sici)1097-4636(199604)30:4<463::aid-jbm4>3.0.co;2-n

Cited by 164 publications

(14 citation statements)

References 39 publications

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“…It has been demonstrated that the cellular response to wear debris varies with the size, shape, composition, charge and concentration of particles (36,37). Furthermore, particle phagocytosis represents an important component of the cellular response to implants; thus, the size of wear particles may be a significant factor affecting osteolysis.…”

Section: Discussionmentioning

confidence: 99%

Metallic wear debris collected from patients induces apoptosis in rat primary osteoblasts via reactive oxygen species‑mediated mitochondrial dysfunction and endoplasmic reticulum stress

et al. 2019

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Although total hip arthroplasty is considered to be an effective surgical procedure for treating hip joint diseases, it is hindered by implant wear debris, which induces aseptic loosening. Various cell types are involved in this pathogenesis; however, the interactions between wear debris and osteoblasts, which serve a crucial role in bone formation, have not been clearly illustrated. In the present study, minor metallic wear particles were collected from the interfacial membrane around loosened implants of patients, and the biological effects of these particles on rat primary osteoblasts were then explored. The results demonstrated that metallic wear debris was able to induce the apoptosis of treated cells in a concentration- and time-dependent manner. Furthermore, it was identified that reactive oxygen species (ROS) generation increased, the mitochondrial membrane potential collapsed, and the mitochondria-caspase-dependent and endoplasmic reticulum (ER) stress apoptotic pathways were activated following metallic wear debris application. In addition, apoptosis and associated pathways were inhibited by the use of N-acetyl-L-cysteine, an antioxidant that suppresses ROS production, indicating that the ROS generation triggered ER stress, mitochondrial dysfunction and downstream cascades that contributed to cell apoptosis. These findings suggest that metallic wear debris-induced ROS serve an important role in the apoptosis of osteoblasts. This provides a valuable insight, not only into understanding the mechanisms underlying the involvement of osteoblasts in osteolysis, but also into a potential novel therapeutic approach to treat implant aseptic loosening.

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Section: Discussionmentioning

confidence: 99%

Metallic wear debris collected from patients induces apoptosis in rat primary osteoblasts via reactive oxygen species‑mediated mitochondrial dysfunction and endoplasmic reticulum stress

et al. 2019

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“…As protein adsorption is known to vary based on material properties, three model polymers with distinct surface properties were investigated to determine whether the TLR2-dependent NF-κB/AP-1 activity observed on lysate-adsorbed surfaces was a robust effect . TCPS, PMMA, and PDMS were selected for their simple, nondegradable chemistry and widespread use in protein adsorption − and macrophage activation − literature, as the primary focus on the study was the cellular response to different adsorbed protein layers. Furthermore, PMMA and PDMS are clinically relevant biomaterials with well-characterized FBR. − PMMA is a moderately hydrophobic polymer (WCA of 68–74°) , that is rigid and stiff at body temperature ( T g = 105 °C for spin-coated thin films) .…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 2-Dependent NF-κB/AP-1 Activation by Damage-Associated Molecular Patterns Adsorbed on Polymeric Surfaces

McKiel

Fitzpatrick

2018

ACS Biomater. Sci. Eng.

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The foreign body reaction is a chronic inflammatory response to an implanted biomaterial that ultimately leads to fibrous encapsulation of the implant. It is widely accepted that the host response to implanted biomaterials is largely dependent on the species and conformations of proteins adsorbed onto the material surface due to the adsorbate's role in mediating cellular interactions with the implanted material. While the cellular response to adsorbed serum-derived proteins has been studied extensively, the presence of endogenous, matrix-and cell-derived mediators of inflammation within the adsorbed protein layer and their impact on cell−material interactions is not well-understood. Damage associated molecular patterns (DAMPs) are endogenous ligands released by stressed or damaged tissues to stimulate sterile inflammatory responses via Toll-like receptors (TLRs) and other pattern recognition receptors. The present study investigated the potential role of tissue-derived, pro-inflammatory stimuli in macrophage responses to biomaterials using cell lysate as a complex source of cell-derived DAMPs and poly(methyl methacrylate) (PMMA) and polydimethylsiloxane (PDMS) films as model biomaterials. We show that lysate-adsorbed PMMA and PDMS surfaces strongly induced NF-κB/AP-1 transcription factor activity and pro-inflammatory cytokine secretion in the RAW-Blue macrophage cell line compared to serum-adsorbed surfaces. Lysate-dependent NF-κB/AP-1 activation and cytokine expression were strongly attenuated by TLR2 neutralizing antibodies, while TLR4 inhibition resulted in a modest reduction. These data suggest that DAMPs, in their adsorbed conformations on material surfaces, may play a significant role in macrophage activation through TLR signaling, and that TLR pathways, particularly TLR2, merit further investigation as potential therapeutic targets to modulate host responses to implanted biomaterials.

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“…Alveolar macrophages phagocytise spherical particles of 1-2 μm most effectively and uptake has been seen up to 5 μm [29]. In vitro, particles of 300 nm are less well phagocytised compared to 5 μm [30]. Particle uptake in macrophages for nano-sized TiO 2 has been estimated to be between 0.06 and 0.12% within 24 hours compared to micron sized particles.…”

Section: Discussionmentioning

confidence: 99%

Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation

et al. 2010

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BackgroundNanoparticle (NP) toxicity testing comes with many challenges. Characterization of the test substance is of crucial importance and in the case of NPs, agglomeration/aggregation state in physiological media needs to be considered. In this study, we have addressed the effect of agglomerated versus single particle suspensions of nano- and submicron sized gold on the inflammatory response in the lung. Rats were exposed to a single dose of 1.6 mg/kg body weight (bw) of spherical gold particles with geometric diameters of 50 nm or 250 nm diluted either by ultrapure water or by adding phosphate buffered saline (PBS). A single dose of 1.6 mg/kg bw DQ12 quartz was used as a positive control for pulmonary inflammation. Extensive characterization of the particle suspensions has been performed by determining the zetapotential, pH, gold concentration and particle size distribution. Primary particle size and particle purity has been verified using transmission electron microscopy (TEM) techniques. Pulmonary inflammation (total cell number, differential cell count and pro-inflammatory cytokines), cell damage (total protein and albumin) and cytotoxicity (alkaline phosphatase and lactate dehydrogenase) were determined in bronchoalveolar lavage fluid (BALF) and acute systemic effects in blood (total cell number, differential cell counts, fibrinogen and C-reactive protein) 3 and 24 hours post exposure. Uptake of gold particles in alveolar macrophages has been determined by TEM.ResultsParticles diluted in ultrapure water are well dispersed, while agglomerates are formed when diluting in PBS. The particle size of the 50 nm particles was confirmed, while the 250 nm particles appear to be 200 nm using tracking analysis and 210 nm using TEM. No major differences in pulmonary and systemic toxicity markers were observed after instillation of agglomerated versus single gold particles of different sizes. Both agglomerated as well as single nanoparticles were taken up by macrophages.ConclusionPrimary particle size, gold concentration and particle purity are important features to check, since these characteristics may deviate from the manufacturer's description. Suspensions of well dispersed 50 nm and 250 nm particles as well as their agglomerates produced very mild pulmonary inflammation at the same mass based dose. We conclude that single 50 nm gold particles do not pose a greater acute hazard than their agglomerates or slightly larger gold particles when using pulmonary inflammation as a marker for toxicity.

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Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophagesin vitro

Cited by 164 publications

References 39 publications

Metallic wear debris collected from patients induces apoptosis in rat primary osteoblasts via reactive oxygen species‑mediated mitochondrial dysfunction and endoplasmic reticulum stress

Metallic wear debris collected from patients induces apoptosis in rat primary osteoblasts via reactive oxygen species‑mediated mitochondrial dysfunction and endoplasmic reticulum stress

Toll-like Receptor 2-Dependent NF-κB/AP-1 Activation by Damage-Associated Molecular Patterns Adsorbed on Polymeric Surfaces

Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation

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