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Effect of reinforcement particle size on in vitro behavior of beta-tricalcium phosphate-reinforced high-density polyethylene: a novel orthopedic composite.

Beta-tricalcium phosphate-reinforced high-density polyethylene (beta-TCP/HDPE) is a new biomaterial, which was made to simulate bone composition and study its capacity to act like bony tissues. This material was produced by replacing mineral component and collagen soft tissue of bone with beta-TCP and HDPE, respectively. The biocompatibility of composite samples with different volume fractions of TCP (20, 30, and 40 vol %) and two different particle sizes (80-100 and 120-140 mesh size) was examined in vitro using the osteoblast cell line G-292 by proliferation, alkaline phosphatase (ALP) production, and cell adhesion assays. Cell-material interaction on the surface of the composites was observed by scanning electron microscopy (SEM). The effect of beta-TCP particle size on behavior of the osteoblast cell line was compared between two groups of the composite samples containing smaller and larger reinforcement particle sizes as well as with those of a negative control. In general, results showed that the composite samples containing larger particles supported a higher rate of proliferation and ALP production by osteoblast cells after 3, 7, and 14 days of incubation compared to the composite samples with smaller particle size and control. Furthermore, more cells were attached to the surface of composite samples containing larger particle size when compared to the smaller particle size composites (p<0.05). This number was nearly equal with numbers adhered on negative control [tissue culture polystyrene (TPS)] and significantly higher in comparison with composite control [polyethylene (PE)] (p<0.05). Adhered cells presented a normal morphology by SEM and many of the cells were seen to be undergoing cell division. These findings indicate that beta-TCP/HDPE composites are biocompatible, nontoxic, and in some cases, act to stimulate proliferation of the cells, ALP production, and cell adhesion when compared to the control counterparts. Furthermore, beta-TCP/HDPE samples with larger reinforcement particle size were shown to possess better biological properties.

Bone Substitutes↗

Migration of polyethylene debris along well-fixed cemented implants.

Implants, consisting of smooth Inox cylinders, were cemented into the lower femur and upper tibia of nine sheep to study the distal migration of polyethylene particles. Some implants had a titanium-bead porous coat at the proximal end. These were of three types: In the first type, the porous coat was covered with hydroxyapatite to obtain a bony seal; the second type was prepared for a polymethylmethacrylate seal; in the third type, the porous zone was surrounded by a 2-mm-thick space to allow the formation of a fibrous seal. Small polyethylene particles were injected into the knees once a week during the third and fourth months after implantation. The animals were euthanized 2 months later. Major longitudinal sections of the implants and the surrounding bone were examined under a polarized light microscope. Birefringent particles were counted at the cement-bone and cement-implant interfaces. Osteolysis was not observed. None of the seals significantly decreased the migration of particles around the cemented part of the implants. Particles were observed in cement fissures and vacuoles. They migrated at both interfaces and in the bone itself. They were visible in marrow spaces between bone trabeculae.

Animals↗

Migration of polyethylene particles around nonloosened cemented femoral components from a total hip arthroplasty-an autopsy study.

Three cemented femoral components from total hip arthroplasties retrieved at autopsy were examined in regard to the migration of birefringent polyethylene particles across the fixation interfaces. They were obtained from two patients who died from unrelated causes. They had been in place, respectively, for 8 and 9 years (first patient) and for 9 years (second patient). Osteolysis was present in the acetabular side only. The femoral components were not loosened. Histologic sections were performed at four levels of the femoral components, and polyethylene particles were counted with the use of a semiautomatic image analyzer. Sections below the tip of the stem were treated by deorganification and the lysate was centrifuged in the attempt to isolate wear debris. Particles were found at both interfaces (bone-cement and metal-cement) and in the cancellous bone between the trabeculae. They were also present in the Haversian canals of the cortical bone. Particles of various sizes were found in the medullary canal beneath the tip of the stem. In scanning electron microscopy, they appeared to have irregular shapes. Wear debris can migrate across the cement-bone interface of nonloosened implants. They appear to progress through the porosity of the cancellous bone.

Aged↗

Molecular orientation of ultrahigh molecular weight polyethylene induced by various sliding motions.

Wear and wear debris of ultrahigh molecular weight polyethylene (UHMWPE) in joint replacements have been recognized as one of the major contributors to the failure of orthopedic implants. The detailed wear mechanism of polyethylene under biomechanic motions is not well understood. In simulation wear bench tests, it was found that unidirectional sliding produces the least amount of wear, reciprocating motion increases wear significantly, and cross-shear motion (similar to hip and knee joint motion in the human body) produces the highest amount of wear. Conventional wear theories are inadequate to explain this observation. This study utilizes resonant absorption of linearly polarized soft X-rays at a synchrotron radiation beam line to measure the molecular orientation of a UHMWPE surface layer subjected to different wear motions. Carbon-K-edge partial-electron-yield X-ray absorption measurements were done on the worn UHMWPE samples. X-ray absorption measurements show conclusively that the molecular chains of UHMWPE align preferentially parallel to the direction of sliding. Examination under various wear motions showed that unidirectional shear produced the maximum chain orientation, whereas cross-shear wear motions produced the least amount of orientation. When polymeric chains align, the surface layer tends to be more brittle and hard, thus resisting wear. When they do not align, loose chains may be subjected to both Mode I and Mode II fracture, hence increasing the wear rate. This molecular alignment observation may offer an explanation of why different wear motions have different wear characteristics.

Humans↗

Opsonization of polyethylene wear particles regulates macrophage and osteoblast responses in vitro.

The cellular reaction to wear debris may result in the failure of an artificial joint's fixation to the skeleton. The influence of debris opsinization on cell activity has received little attention. This study seeks to establish whether different proteinaceous culture environments may invoke variant cellular responses to debris challenge. Consideration of the zeta potential of a low density polyethylene particle group and an ex vitro ultrahigh molecular weight polyethylene particle group revealed that the nature of the protein adsorbants is related to the concentration of the proteins in solution. Furthermore, the composition of the adsorbed layer was shown to vary with the spectra of proteins in solution. In standard cell culture conditions zeta potential approached zero, indicating the high probability of particle agglomeration. Cell challenge studies with U937 macrophages showed that BSA and FCS protein adsorption mediated increased cell adhesion, while bovine IgG showed little change over control values. No changes in behavior of osteoblastic cells were observed in similar experiments.

Adsorption↗

Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery.

In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery.

Administration, Oral↗

Cupric ion release controlled by copper/low-density polyethylene nanocomposite in simulated uterine solution.

The Cu2+ release rate of novel copper/low-density polyethylene composites as an intrauterine device material in the simulated uterine solution was investigated for 280 days. The corrosion products of these composites were identified by the X-ray diffraction method. The distributions of the copper phase and the cuprous oxide phase at different corrosion depths in the composites were measured by the internal standard method. For comparison, copper particles of two sizes were embedded in a polyethylene matrix to form composites. The average copper particle diameter of the nanocomposite was 30 nm, while that of microcomposite was 52 microm. Mechanism of Cu2+ release controlled by the nanocomposite revealed that many clusters composed of copper nanoparticles, which were observed by the field emission scanning electron microscopy in the nanocomposite, led to the formation of large amounts of Cu2O and consequently facilitated the Cu2+ steady release. A scanning electron microscope with energy dispersive X-ray microanalysis mapping technique (SEM/EDX) was employed to measure the corrosion depth and to calculate the life span of the nanocomposite. The result that the nanocomposite displayed a near zero-order release after a month of incubation indicated that the Cu2+ release behavior controlled by nanocomposite was remarkably superior to that by microcomposite.

Biocompatible Materials↗

Comparison of multinucleated cells elicited in rats by particulate bone, polyethylene, or polymethylmethacrylate.

Osteoclasts, the multinucleated resorbing cells of bone, are identified by their characteristic morphology, unique cell membrane specializations, and more recently by the presence of cell surface antigens recognized by monoclonal antibodies. They are derived from mononuclear precursor cells of hematogenous origin. The precise relationship between osteoclasts and other types of tissue giant cells is unknown. This study was designed to examine factors involved in the recruitment and differentiation of multinucleated cells and to investigate the relationship between so-called foreign body giant cells and bone-resorbing osteoclasts. Particles of various materials were implanted into subcutaneous pockets in rats. Histological, histochemical, and electron microscopic evaluations were made of specimens harvested 12 days after implantation. Large, foamy multinucleated cells were evident around particles of devitalized bone, polyethylene, and polymethylmethacrylate. Bone particles showed scalloped surfaces and were partially resorbed. Those cells adjacent to the bone particles stained positive for tartrate-resistant acid phosphatase, in contrast to the multinucleated cells adjacent to the other materials. All the cell types had extensive rough endoplasmic reticulum, abundant mitochondria, cytoplasmic vacuoles and dense bodies, giant centrospheres, and areas of fusion of plasma membranes. Cells in lacunae on the surface of the bone particles showed a clear zone of attachment to the bone substrate and ruffled borders, a feature characteristic of in osso osteoclasts. Although the giant cells occasionally displayed an extensive clear zone of attachment to the polyethylene and polymethylmethacrylate particles, no ruffled borders were detected. The results of these studies show that the multinucleated cells elicited in response to different materials, although sharing many common features, do demonstrate certain features that are substrate specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Cyclic compressive loading results in fatigue cracks in ultra high molecular weight polyethylene.

Wear damage to the articulating surfaces of total joint components made of ultra high molecular weight polyethylene is associated with a fatigue fracture mechanism, despite the fact that these surfaces are subjected to primarily compressive and compressive-tensile cyclic stresses. The question arises as to whether fatigue cracks will form under such loading conditions. In this study, we experimentally demonstrated that fatigue cracks could be initiated and propagated in notched ultra high molecular weight polyethylene specimens subjected to fully compressive and compressive-tensile cyclic loading. Under these loading conditions, growth of fatigue cracks was limited: the cracks arrested without catastrophic failure of the test specimens. The final length of the crack was dependent on the load ratio of the fatigue cycle; fatigue cracks propagated to greater lengths as the load ratio was increased.

Knee Prosthesis↗

Degradation rate of ultra-high molecular weight polyethylene.

Ultra-high molecular weight polyethylene components for total joint replacement chemically degrade before and after implantation, and the degradation is associated with an increase in density. The goal of this study was to determine the average rate of density change in these components following sterilization by gamma radiation in air as a function of shelf age and implantation time. Using the density gradient column method, density profiles were obtained through the thickness from loaded and unloaded regions of 10 retrieved Insall-Burstein/Posterior-Stabilized II tibial components and one operating-room inventory component for which the initial density profile and patient history (if applicable) were known. The average density of the components increased at a constant rate of 0.000186 g/cc/month during the first 50 months after sterilization (r2 = 0.54) but was not significantly affected by loading (p > 0.05). The quantitative degradation rates may be useful to help verify kinetic models to predict bulk degradative changes on the basis of micro-structural and chemical processes. This research also suggests the hypothesis that degradation of ultra-high molecular weight polyethylene can be modeled in terms of changes in bulk or average properties.

Gamma Rays↗

Prediction of long-term polyethylene wear in total hip arthroplasty, based on early wear measurements made using digital image analysis.

The capability to reliably predict long-term in vivo wear of polyethylene would be of great value for the early identification of problematic total hip designs. Formal quantitative estimates of long-term polyethylene wear were made from a series of 197 patients who had a total hip arthroplasty and who were followed for a minimum of 10 years; the estimates were based on the wear that was apparent radiographically at nominally 2 years after the operation. A newly developed digital image-analysis edge-detection procedure was applied to 1,237 archived follow-up radiographs. The edge-detection measurements were analyzed with a robust regression random-coefficients statistical formulation developed especially to address the distributions of wear rate observed across this population over time. Formal regression equations were reported, which can be used to estimate late-wear depth for a patient radiographed at a 2-year follow-up visit. Series wide, the correlation between predicted and observed wear depths was 0.73 at 4 years, with a correlation decline of approximately 0.03 per additional year.

Aged↗

Effect of molecular weight, calcium stearate, and sterilization methods on the wear of ultra high molecular weight polyethylene acetabular cups in a hip joint simulator.

Orthopaedic surgeons must currently choose from several types of ultra high molecular weight polyethylene acetabular cups that differ in their material properties and in the methods used for their sterilization. Information on the wear resistance of these different cups may help in the selection process. This study included two separate tests for wear run on a hip simulator to investigate the effect of molecular weight, calcium stearate, and sterilization methods on the wear resistance of ultra high molecular weight polyethylene acetabular cups. Test 1 revealed nearly identical wear rates for acetabular cups with molecular weights in two distinct ranges, as well as for cups with molecular weights in the same range but with or without calcium stearate added. In Test 2, cups that were sterilized in air with gamma irradiation exhibited lower rates of wear than those sterilized with ethylene oxide, presumably due to the crosslinking induced by the irradiation. In addition, cups that were irradiated while packed in a partial vacuum to minimize oxygen absorbed in the surface layer initially showed lower rates of wear than those irradiated in air, with the wear rates becoming similar as wear penetrated the more oxidized surface layer and the more crosslinked subsurface region. Because these tests were run a few months after the irradiation, the potential effects of long-term oxidation of any residual free radicals in the irradiated materials could not be taken into account. After artificial aging to accelerate oxidative degradation of the materials, the wear rates could be markedly different. Analyses performed after wear indicated that the irradiated (i.e., crosslinked) cups exhibited a smaller proportion of, as well as shorter, fibrils in the wear debris and an increased crystallinity and melting temperature and that gamma irradiation in the low-oxygen environment reduced the level of oxidation and increased the level of crosslinking in the surface region of the cups.

Acetabulum↗

Polyethylene wear vector in vivo: a three-dimensional analysis using retrieved acetabular components and radiographs.

Polyethylene wear of the acetabular component can be described as one or more vectors. To help clarify the mechanisms of wear advancement in vivo, we used a combination of retrieved implants and radiographs to describe the three-dimensional wear vectors in total hip arthroplasty. The wear vectors in 41 retrieved implants from a single manufacturer were measured with use of the shadowgraph technique, and the spatial orientation of each implant was calculated from serial anteroposterior pelvic radiographs. On the basis of the combination of the wear vector in the implant and implant orientation in the pelvis, the wear vectors in vivo were determined. The mean wear vector was directed 8.1 degree lateral in the coronal plane and 4.1 degree posterior in the sagittal plane. The wear vectors in vivo showed a relatively wide range of directions, not necessarily coinciding with the commonly presumed resultant force in the hip. The wear vectors were not associated with the spatial orientation of the acetabular components, but cups with impingement demonstrated more anterior wear than did those without impingement. Our results suggest that the process of polyethylene wear is not as simple as previously described and that several factors influence advancement of wear in vivo.

Acetabulum↗

Alterations in surface geometry in retrieved polyethylene glenoid component.

This study characterized and quantified the changes found in retrieved glenoid polyethylene components found at revision total shoulder arthroplasty (TSA). Twenty components obtained at revision TSA were evaluated, all from a system (Global, DePuy, Warsaw, IN) with a glenoid radius of curvature 3 mm greater than that of the humeral head. Laser surface scanning provided three-dimensional analysis of the surface of the glenoid component. Scans of unused components of similar sizes enabled determination of the changes occurring after implantation. Alterations in radius of curvature were noted in every glenoid. All showed loss of the balance stability angle (BSA, the maximal angle that the net humeral joint reaction force can make with the glenoid center line before the humeral head would dislocate) of at least 5 degrees in one or more directions. Increase in BSA in one direction was seen in 11 of the components. In five of these, the increase was associated with a reduction of the local radius to match that of the humeral component. Glenoid surface morphology and stability can be changed by in vivo use. While correlation with clinical instability in the patients from whom the implants were obtained was not possible, many of the observed changes in surface morphology are of sufficient magnitude to compromise the contribution of the glenoid surface to shoulder stability. Three patterns of wear were identified: "humeral" that showed loss of the mismatch between the humeral and glenoid radii of curvature (5 of 20 components), "diffuse" that showed broad surface irregularity (18 of 20), and "rim" wear with loss of the polyethylene rim of the component (14 of 20). More than one type of wear was possible within a single glenoid.

Arthroplasty, Replacement↗

Effect of polyethylene glycol 4000 on dissolution properties of sulfathiazole polymorphs.

The dissolution rates of the two polymorphic forms of sulfathiazole containing polyethylene glycol 4000 were significantly different in water. The effect of agitation on the dissolution rates also was studied. At higher stirring speeds, the dissolution rates of the stable form were affected more than the metastable form. A high concentration of polyethylene glycol 4000 seemed to affect the dissolution properties of the metastable polymorph more than the stable polymorph.

Isomerism↗

Pharmaceutical applications of solid dispersion systems: X-ray diffraction and aqueous solubility studies on griseofulvin-polyethylene glycol 6000 systems.

The X-ray diffraction method was used to characterize physiochemical properties of griseofulvin dispersed in polyethylene glycol 4000 and 6000. Results indicate a negligible or very limited solid solubility of griseofulvin in the pulverized solid dispersions. Pulverization and aging had pronounced effects on the X-ray diffraction spectrum. Results from aqueous solubility studies of griseofulvin in various concentrations of polyethylene glycol 6000 further indicate weak or insignificant interactions between the drug and the carrier. Mechanisms are postulated to account for the reported marked enhancement of dissolution rates and oral adsorption of griseofulvin dispersed in these carriers.

Chemistry, Pharmaceutical↗

Effect of aging on hydrocortisone-polyethylene glycol 4000 and hydrocortisone-polyvinylpyrrolidone dispersions.

Dispersions containing 40% hydrocortisone were prepared by the solvent method in polyethylene glycol 4000. Dispersions in polyvinylpyrrolidone were prepared by slow evaporation of solvent (type A) and by fast evaporation of solvent (type B). These dispersions were stored at 25 degrees C for 30 d. Plots of time required for 50% (t50%) and 70% (t70%) of the hydrocortisone dispersion to dissolve (beaker method) versus time were obtained. Hydrocortisone-polyethylene glycol showed no apparent significant change in either dissolution rate, X-ray spectra, or scanning electron micrographs. Type A dispersions showed an increase in dissolution rate up to 8 d. Type B dispersions showed an initial decrease followed by an increase in dissolution rate. The initial decrease in dissolution rate of type B dispersions is due to hydrocortisone crystallizing out of the polyvinylpyrrolidone matrix. The increased dissolution for both types of polyvinylpyrrolidone dispersions was not expected and is for both types of polyvinylpyrrolidone dispersions was not expected and is explained by an increased proportion of the high-energy amorphous component, based on X-ray spectra. Other possibilities such as the presence of polymorphic forms of hydrocortisone and/or reduction in particle aggregation could not be discounted.

Chromatography, Thin Layer↗

Separation and quantitation of polyethylene glycols 400 and 3350 from human urine by high-performance liquid chromatography.

Polyethylene glycol 3350 (PEG 3350) is useful as an orally administered probe to measure in vivo intestinal permeability to macromolecules. Previous methods to detect polyethylene glycol (PEG) excreted in the urine have been hampered by inherent inaccuracies associated with liquid-liquid extraction and turbidimetric analysis. For accurate quantitation by previous methods, radioactive labels were required. This paper describes a method to separate and quantitate PEG 3350 and PEG 400 in human urine that is independent of radioactive labels and is accurate in clinical practice. The method uses sized regenerated cellulose membranes and mixed ion-exchange resin for sample preparation and high-performance liquid chromatography with refractive index detection for analysis. The 24-h excretion for normal individuals after an oral dose of 40 g of PEG 3350 and 5 g of PEG 400 was 0.12 +/- 0.04% of the original dose of PEG 3350 and 26.3 +/- 5.1% of the original dose of PEG 400.

Adult↗