Poly Methyl Methacrylate Particles Research Articles

Osteoclasts are capable of particle phagocytosis and bone resorption.

Osteoclasts are multinucleated cells specialized for the function of lacunar bone resorption. Although they are known to be capable of phagocytosis of inert particles, it is not known whether this abolishes their ability to respond to hormones or to form resorption lacunae. Human and rat osteoclasts were isolated from giant cell tumours of bone and rat long bones, respectively, and cultured on coverslips and cortical bone slices, both in the presence and in the absence of particles of latex (1 micron diameter) and polymethylmethacrylate (PMMA) (< 50 microns). By light microscopy, it was evident that osteoclasts which had phagocytosed both latex and PMMA particles remained responsive to calcitonin. Osteoclast phagocytosis of particles was also evident on scanning electron microscopy, where it could also be seen that these cells were associated with the formation of resorption lacunae. These findings underline the fact that the osteoclast is a true member of the mononuclear phagocyte system and that phagocytosis does not abrogate either its hormonal response to calcitonin or its highly specialized function of bone resorption. That osteoclasts which have phagocytosed biomaterial particles such as PMMA are still able to carry out lacunar bone resorption is of interest in clinical conditions such as aseptic loosening, where a heavy foreign body particle load is often associated with extensive bone resorption.

Presence of silicon in massive osteolysis after cementless total hip arthroplasty: Case report

Osteolysis associated with artificial joint arthroplasty seems to be the result of particles of wear debris (from ultra-high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA), and metals), causing a macrophage response. Silicon particles, as residual contaminants embedded in the surface of both textured metal implants and polyethylene sockets, may be a factor in osteolysis. We present the case of a 57-year-old woman who had massive and aggressive osteolysis. The osteolytic lesion was isolated in the greater trochanter region 5 years after she had had primary cementless total hip arthroplasty (Cobalt-chromium alloy). There were no signs of mechanical loosening, but she experienced moderate pain. Under a polarized microscope and scanning electron micrography, a biopsied specimen from the osteolytic lesion revealed conglomerates of UHMWPE particles of various sizes between proliferated synovium-like cells. Quantitative energy-dispersive X-ray analysis focused on the conglomerates of UHMWPE particles demonstrated a marked presence of silicon. Although the definitive causative factor for a 1he osteolysis was regarded as a foreign-body reaction induced by UHMWPE particles, the presence of silicon was interesting in terms of the pathogenesis of osteolysis associated with artificial joint surgery.

Elastic-Like and Viscous-Like Components of the Shear Viscosity for Nearly Hard Sphere, Brownian Suspensions

The shear properties of Brownian, rigid spheres consisting of sterically stabilized, crosslinked polymethylmethacrylate (PMMA) particles were studied in suspension. Three different volume fractions were used to carry out this study. The suspensions’ elastic-like and viscous-like components of the shear stress were measured by a recently developed technique utilizing cessation of steady shear. The elastic-like viscosity component, or the amount of stress retained at the instant of cessation divided by the shear rate, due to Brownian and possible interparticle forces, decreased in magnitude over the entire range of shear rates used (shear thinning). The decay of the elastic-like stress with time after cessation of flow was also analysed and found to fit a power law relation. The viscous-like component, or the amount of stress lost at the instant of cessation divided by the shear rate, is related to hydrodynamic interactions between and drag on particles and remained essentially constant with shear rate. These data are the first of this kind gathered for a model hard sphere system (i.e., mechanical means) and agrees well with results of Bender and Wagner (J. Colloid Interface Sci.172,171 (1995) who used an optical technique.

RADIO-OPAQUE AGENTS IN BONE CEMENT INCREASE BONE RESORPTION

A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO4) and zirconium dioxide (ZrO2) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO4 or ZrO2, however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO4 were associated with 50% more bone resorption than those containing ZrO2. Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing is BaSO4 likely to be associated with more osteolysis than that containing ZrO2.

Radio-opaque agents in bone cement increase bone resorption.

A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO4) and zirconium dioxide (ZrO2) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO4 or ZrO2, however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO4 were associated with 50% more bone resorption than those containing ZrO2. Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing BaSO4 is likely to be associated with more osteolysis than that containing ZrO2.

Inflammatory response to implant particulates in a macrophage/osteoblast coculture model.

The purpose of this study was to further define the cellular response to titanium and polymethylmethacrylate (PMMA) particles in aseptic loosening, and to determine if the use of pamidronate may be effective in inhibiting bone resorption associated with this response. Macrophages and osteoblasts were cocultured to simulate the environment around an aseptically loose prosthesis. Macrophages were plated on the bottom of six well plates and osteoblasts were plated on culture dish inserts, and placed into the wells with the macrophages. Incubation of macrophages with PMMA in this system led to release of prostaglandin E (PGE2), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-6 (IL-6). Incubation with titanium led to release of tumor necrosis factor (TNF) and IL-6. Exposure of calvaria to media from cells exposed to either PMMA or titanium led to release of calcium 45. Incubation of calvaria with pamidronate was able to inhibit release of calcium 45 associated with exposure to the macrophage/osteoblast/particle conditioned medium. Bone resorption at the interface between implant and bone is a consistent feature leading to loosening of orthopedic implants. By inhibiting bone resorption associated with the inflammatory response to implant particulates, pamidronate or other bisphosphonates may have clinical utility in the treatment or prevention or aseptic loosening.

Production of polymethylmethacrylate particles by dispersion polymerization in aqueous media with ceric ammonium nitrate

Polymethylmethacrylate particles with narrow size distributions with different sizes in the range of 1.25–4.58 μm were produced by dispersion polymerization of methylmethacrylate (MMA) in ethanol/water media, by using 2,2′-azobisisobutyronitrile (AIBN) (as an initiator), (PVP) poly(vinyl pyrrolidone) (as a stabilizer), and ceric ammonium nitrate (CAN) (as a coinitiator and also as a costabilizer). Particle size was increased by increasing the initiator concentration and the ethanol: water ratio, and by decreasing the monomer: dispersion medium ratio and the PVP and CAN concentrations. The addition of CAN in the recipe of the MMA polymerization improved the monodispersity, and also increased the monomer conversion rate. © 1996 John Wiley & Sons, Inc.

Production of polymethylmethacrylate particles by dispersion polymerization in aqueous media with ceric ammonium nitrate

Production of polymethylmethacrylate particles by dispersion polymerization in aqueous media with ceric ammonium nitrate

In vivo inflammatory response to silicone elastomer particulate debris

Silicone elastomer particles (Silastic silicone elastomer, Dow Corning, Midland, MI), polymethylmethacrylate particles, and monosodium urate particles smaller than 10 microns were injected into a rat subcutaneous air pouch lined with synovial membrane-like cells. Inflammatory exudate from the air pouch was retrieved at 6 hours, 24 hours, 48 hours, and 72 hours after injection. White blood cell count, tumor necrosis factor, and prostaglandin E2 were measured in the exudate. White blood cell and tumor necrosis factor levels in the exudate were the highest for the silicone group at 6 and 24 hours. Prostaglandin E2 was also significantly higher in the silicone group at 24 hours. We conclude that the acute inflammation is particle-type specific and that Silicone elastomer particles are acutely inflammatory.

The immune response to implant materials in humans.

The etiology of aseptic loosening of prosthetic joint replacement components is unclear. Implant materials have been considered biologically inert, but recently studies indicate that inflammatory reactions directed against the implanted materials may contribute to aseptic loosening. Data suggesting a progression from a simple inflammatory reaction to complex immune responses against the biomaterials are reviewed. The cellular responses to particles of polymethylmethacrylate, ultrahigh molecular weight polyethylene, and alloys of cobalt-chromium and titanium were assayed in vitro to determine cell proliferation in patients with underlying diagnoses of osteoarthrosis, rheumatoid arthritis, and avascular necrosis who had joint replacement. Control populations were provided by patients with similar diagnoses who were preoperative surgical candidates. The underlying diagnoses did not seem to influence responses to particle stimulation. Elevated responses to both acrylic and cobalt-chromium were observed in patients with aseptically loosened prostheses. These findings suggest that the development of a cellular response to particulate debris may be significant in the pathogenesis of aseptic loosening.

Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophages in vitro.

This study investigated effects of different sizes, concentrations, volumes, and surface areas of polymethylmethacrylate (PMMA) particles on human macrophages. Adherent peripheral blood monocytes isolated from five healthy individuals were exposed for 48 h to phagocytosable (0.325 micron and 5.5 microns) and nonphagocytosable (200 microns) spherical particles. Each particle size was tested over a range of concentrations (10(4)-10(11) particles per milliliter [0.325 micron], 10(2)-10(7) particles per milliliter [5.5 microns], 10(1)-10(4) particles per milliliter [200 microns]) to provide overlap in number, volume, and surface area. Primary human monocyte/macrophages were cultured in macrophage serum-free medium and 5% fetal calf serum. Macrophage viability was assessed by 3H-thymidine uptake and activation was quantified by release of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, prostaglandin E2 (PGE2), and the lysosomal enzyme hexosaminidase. Medium alone served as a negative control; lipopolysaccharide (10 micrograms/mL) was also tested. PMMA particles were not toxic to human macrophages at any concentration tested. The smallest phagocytosable particles (0.325 micron) stimulated the release of interleukin-1 beta, interleukin-6, prostaglandin E2, and hexosaminidase at concentrations of 10(10)-10(11) particles/mL. The release of cytokines, PGE2, and hexosaminidase depended on the size, concentration, surface area, and volume of the phagocytosable particles. This study demonstrates that PMMA particle load Mi.e., the concentration of phagocytosable particles per tissue volume, characterized by size, surface area, and volume, rather than simply particle number-determines the degree of macrophage activation.

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

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

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND PROSTAGLANDINS

The objective of this study was to determine the effects of orally administered misoprostol and diclofenac on inflammation caused by particulates in the rat subcutaneous air-pouch model. Subcutaneous air pouches were formed in male Sprague-Dawley rats. The animals were premedicated by gavage with either saline, diclofenac, misoprostol, or both diclofenac and misoprostol. The air pouches were injected with either polymethyl methacrylate particles or monosodium urate crystals, and the pouch fluids were obtained at 1, 6, 24, 48, and 72 h. Leukocyte influx, tumor necrosis factor, neutral metalloprotease activity, and prostaglandin E(2) levels were measured. It was determined that leukocyte influx was inhibited by diclofenac in the acute inflammation caused by monosodium urate crystals only. In all animals receiving diclofenac, prostaglandin E(2) (PGE(2)) levels were reduced, whereas tumor necrosis factor levels were elevated. The elevation of tumor necrosis factor was prevented by the addition of misoprostol. It is concluded that the oral administration of diclofenac or misoprostol can affect levels of specific mediators involved in particulate-induced inflammation in the subcutaneous air pouch.

Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor.

To determine the influence of polymethylmethacrylate (PMMA) wear particles on macrophage-osteoclast differentiation, PMMA particles were added to mouse monocytes which were cocultured with UMR 106 osteoblast-like cells in the presence of 1,25 dihydroxy vitamin D3[1,25(OH)2D3] for up to 7 days on glass coverslips and for up to 14 days on human cortical bone slices. An increase in osteoclast differentiation, as evidenced by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and the extent of lacunar bone resorption, was observed in monocyte cultures to which PMMA had been added. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) added to these cocultures caused considerably less expression of TRAP and significant inhibition of lacunar bone resorption. This inhibitory effect was reversed by the addition of specific neutralizing antibodies to LIF and IL-4. These findings show that PMMA-wear particle-associated macrophages exhibit an enhanced capacity for differentiation to osteoclastic bone-resorbing cells.

Investigation of the Codeposition of Polymer Lattices With Copper on a Rotating Disk Electrode

ABSTRACTThis article involves the study of the electrodeposition of composite coatings that form when colloidal particles deposit onto an electrode at which metal electrodeposition simultaneously occurs. The codeposition process of polystyrene (PS) and polymethylmethacrylate (PMMA) particles from a copper plating bath on a rotating disk electrode (rde) was investigated both theoretically and experimentally. The influence of the fluid flow velocity, density, mean size and zeta-potential of the particles, viscosity and temperature of the plating bath on the deposition rate of particles is studied using the theoretical model. The predictions of the model are compared with experimental results.

Human monocytes stimulation by particles of hydroxyapatite, silicon carbide and diamond: in vitro studies of new prosthesis coatings

Aseptic loosening due to wear and debris formation constitutes the major problem in longevity of joint replacements. Diamond coated onto the prosthesis surface may reduce wear, owing to its excellent tribological properties. A thin diamond coating may be brittle, and we plan eventually to reinforce it with silicon carbide whiskers (SiC). In the present study we compared particles of diamond, SiC and hydroxyapatite (HA) in serum-free cultures of human monocytes. All particles were found to be phagocytozed, and monocyte morphology changed except after the ingestion of diamond. Interleukin-1β production was increased on average 30-fold and 38-fold in cultures exposed to HA and SiC, respectively, compared to control and diamond cultures ( n = 6). Addition of the phagocytosis inhibitor cytochalasin B inhibited the morphological changes of the monocytes and reduced interleukin-1β production. In some experiments particles of polymethylmethacrylate were also included, and the interleukin-1β stimulation was in the same range as after HA and SiC stimulation. The results show that diamond particles in serum-free monocyte culture are inert, while SiC and HA have a stimulatory effect comparable to polymethylmethacrylate. With its excellent tribological and biocompatible properties, future studies with diamond coating are warranted.

Role of tumor necrosis factor alpha in particulate‐induced bone resorption

The purpose of this study was to determine the role of tumor necrosis factor alpha in bone resorption secondary to mediator release from macrophages exposed to cement particles. The J774 mouse macrophage cell line was exposed to polymethylmethacrylate particles for 24 hours and the resulting conditioned medium was analyzed for prostaglandin E2, tumor necrosis factor alpha, interleukin-1 alpha and beta, and the ability to stimulate release of prostaglandin E2 and 45Ca from radiolabeled mouse calvaria. Macrophage exposure to polymethylmethacrylate particles led to a 9-fold increase in release of tumor necrosis factor alpha (p < 0.01), but did not lead to a significant increase in release of prostaglandin E2, interleukin-1 alpha, or interleukin-1 beta when compared to unexposed cells. Exposure of the macrophages to polymethylmethacrylate particles over a time course from 30 minutes to 96 hours led to an increase in the release of tumor necrosis factor alpha that was initially detected at 30 minutes and was maximum at 48 hours. Incubation of the macrophage-polymethylmethacrylate conditioned medium with rat calvaria significantly increased the release of 45Ca and prostaglandin E2 from the bone. To study the role of release of tumor necrosis factor alpha in bone resorption, the macrophage-polymethylmethacrylate conditioned medium was then preincubated with anti-tumor necrosis factor alpha antibody prior to exposure of the conditioned medium to the calvaria. This preincubation was successful in significantly inhibiting 45Ca release by calvaria (p <0.01) to levels that were not significantly different from the levels of release by unexposed calvaria. Tumor necrosis factor alpha appears to play a critical role in initiating particulate-induced bone resorption. Exposure of macrophages to polymethylmethacrylate particles leads to a significant release of tumor necrosis factor alpha in a time-dependent fashion. This macrophage-polymethylmethacrylate conditioned medium stimulated release of prostaglandin E2 and bone resorption in bone organ culture. The addition of anti-tumor necrosis factor alpha antibody to this in vitro system inhibited the bone resorption stimulated by the macrophage-polymethylmethacrylate conditioned medium and partially suppressed the production of prostaglandin E2. The sequence of events in this model for particulate-induced bone resorption appears to be initiated by the production of tumor necrosis factor alpha by the macrophage, followed by production of prostaglandin E2 by cells in bone, and then by bone resorption.

Tissue response to particulate polymethylmethacrylate in mice with various immune deficiencies.

We examined the tissue response to subcutaneous injections of particulate polymethylmethacrylate powder in fully immunocompetent C3Hf/Sed mice as well as three strains of mice with different levels of lymphocyte dysfunction. Five weeks after the injection, we found clearly demarcated granulomas. Histological and immunohistochemical studies showed that these granulomas were similar among all strains, with either paucity or absence of lymphoid cells. In situ hybridization with use of complementary RNA probes indicated that macrophages were synthesizing interleukin-1 beta messenger RNA (mRNA), a marker of macrophage activation, and a cytokine implicated in pathological bone resorption. We concluded that, in mice, there is a lymphocyte-independent pathway of macrophage activation in response to particulate polymethylmethacrylate. This suggests that the foreign-body response to particulate orthopaedic biomaterials is macrophage-initiated and maintained and that lymphocytes are not essential to this response, although they may modulate it.

Short-time Brownian motion in colloidal suspensions: Experiment and simulation.

We used dynamic light scattering (DLS) and computer simulations based on the fluctuating lattice Boltzmann equation (LBE) method to study the short-time Brownian dynamics of colloidal particles that interact like hard spheres. The dynamics are characterized by a Q-vector-dependent diffusion coefficient ${\mathit{D}}_{\mathit{S}}$(Q). Using DLS, we have mesaured ${\mathit{D}}_{\mathit{S}}$(Q) in the vicinity of the main (first) peak in the structure factor S(Q) for samples of poly-methylmethacrylate particles at volume fractions \ensuremath{\varphi} ranging from dilute up to the disorder-order transition (i.e., crystallization at \ensuremath{\varphi}=0.494). In addition we have determined the short-time self-diffusion (${\mathit{D}}_{\mathit{S}}^{\mathit{S}}$) and collective-diffusion ${\mathit{D}}_{\mathit{S}}^{\mathit{C}}$ coefficients. We have extracted the same quantities from simulations of equilibrium configurations of hard spheres using a fluctuating lattice Boltzmann equation method for the fluid phase coupled to Newtonian mechanics for the colloidal particles. For all samples studied, close quantitative agreement is found between the results of the DLS experiments and the LBE simulations.

Mechanisms of cellular recruitment in aseptic loosening of prosthetic joint implants.

The association of macrophages engaged in polymethylmethacrylate (PMMA) particle phagocytosis with pockets of inflammatory cells is a pathognomonic feature of the aseptically loose interface not present at the well-fixed interface. The mechanism by which the presence of PMMA particles leads to cellular recruitment, bone resorption, and ultimate loosening is poorly understood. Granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 6 (IL-6), cytokines released by osteoblasts, stimulate the recruitment of macrophages into sites of inflammation. We show that exposure of macrophages to PMMA particles stimulated release of tumor necrosis factor (TNF), but no increase in prostaglandin E2 (PGE-2) or interleukin 1. Incubation of osteoblasts with conditioned medium from macrophages exposed to PMMA particles led to release of GM-CSF, IL-6, and PGE-2. Incubation of the PMMA/macrophage medium with antibodies to TNF prior to osteoblast exposure inhibited release of GM-CSF, IL-6, and PGE-2 by the osteoblasts. Our data demonstrate that exposure of macrophages to PMMA particles leads to the release of TNF which then stimulates osteoblasts to produce GM-CSF, IL-6 and PGE-2. Based upon the results of this study , we propose that the process of cellular recruitment in aseptic loosening is initiated when the mechanical failure of the cement mantle leads to the production of PMMA particles. These particles are phagocytized by macrophages leading to the production of TNF. TNF stimulates surrounding osteoblasts to produce GM-CSF, IL-6, and PGE-2 which leads to recruitment of macrophages and osteoclasts into the area of the bone-cement interface. The recruitment of these cells potentiates this process leading to bone resorption and ultimately, clinical loosening of prosthetic joint implants.