Ultra-high Molecular Weight Polyethylene Debris Research Articles

Identification of IL-27 as potent regulator of inflammatory osteolysis associated with vitamin E-blended ultra-high molecular weight polyethylene debris of orthopedic implants

Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. Statement of SignificanceAseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.

Implant wear induced inflammation is mitigated in CX3CR1−/− mice

Wear debris-induced monocyte recruitment plays a key role in the formation of chronic periprosthetic tissue inflammation associated with aseptic loosening. The purpose of this study was to investigate the role(s) of chemokine receptor CX3CR1 in ultra high molecular weight polyethylene (UHMWPE) particle-induced tissue inflammation using a murine air pouch model developed in CX3CR1 knockout (CX3CR1(-/-) ) mice. UHMWPE debris or saline were introduced into established air pouches on CX3CR1(-/-) and CX3CR1(+/+) mice. Pouch tissues were collected 7 days after UHMWPE inoculation. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in CX3CR1(+/+) mice, as manifested by inflammatory cellular infiltration (mainly macrophages), pouch tissue proliferation, and increased gene expression of IL-1ß and TNFα. UHMWPE-induced inflammation was significantly mitigated in CX3CR1(-/-) mice, as manifested by reduction of tissue inflammation (pouch thickness and cell density), inflammatory cytokine production (IL-1ß and TNFα) and macrophage accumulation. The observations support the hypothesis that the activation of the CX3CR1 chemokine pathway contributes to the severity of UHMWPE particle-induced tissue inflammation, and suggests that CX3CR1 signaling is involved in the recruitment of monocytes to the wear debris-containing inflammatory tissues. Blocking of CX3CR1 pathway may represent a viable therapeutic approach to the prevention and treatment of patients with aseptic loosening.

Epidural application of spinal instrumentation particulate wear debris: a comprehensive evaluation of neurotoxicity using an in vivo animal model

The introduction and utilization of motion-preserving implant systems for spinal reconstruction served as the impetus for this basic scientific investigation. The effect of unintended wear particulate debris resulting from micromotion at spinal implant interconnections and bearing surfaces remains a clinical concern. Using an in vivo rabbit model, the current study quantified the neural and systemic histopathological responses following epidural application of 11 different types of medical-grade particulate wear debris produced from spinal instrumentation. A total of 120 New Zealand White rabbits were equally randomized into 12 groups based on implant treatment: 1) sham (control), 2) stainless steel, 3) titanium alloy, 4) cobalt chromium alloy, 5) ultra-high molecular weight polyethylene (UHMWPe), 6) ceramic, 7) polytetrafluoroethylene, 8) polycarbonate urethane, 9) silicone, 10) polyethylene terephthalate, 11) polyester, and 12) polyetheretherketone. The surgical procedure consisted of a midline posterior approach followed by resection of the L-6 spinous process and L5-6 ligamentum flavum, permitting interlaminar exposure of the dural sac. Four milligrams of the appropriate treatment material (Groups 2-12) was then implanted onto the dura in a dry, sterile format. All particles (average size range 0.1-50 μm in diameter) were verified to be endotoxin free prior to implantation. Five animals from each treatment group were sacrificed at 3 months and 5 were sacrificed at 6 months postoperatively. Postmortem analysis included epidural cultures and histopathological assessment of local and systemic tissue samples. Immunocytochemical analysis of the spinal cord and overlying epidural fibrosis quantified the extent of proinflammatory cytokines (tumor necrosis factor-α, tumor necrosis factor-β, interleukin [IL]-1α, IL-1β, and IL-6) and activated macrophages. Epidural cultures were negative for nearly all cases, and there was no evidence of particulate debris or significant histopathological changes in the systemic tissues. Gross histopathological examination demonstrated increased levels of epidural fibrosis in the experimental treatment groups compared with the control group. Histopathological evaluation of the epidural fibrous tissues showed evidence of a histiocytic reaction containing phagocytized inert particles and foci of local inflammatory reactions. At 3 months, immunohistochemical examination of the spinal cord and epidural tissues demonstrated upregulation of IL-6 in the groups in which metallic and UHMWPe debris were implanted (p < 0.05), while macrophage activity levels were greatest in the stainless-steel and UHMWPe groups (p < 0.05). By 6 months, the levels of activated cytokines and macrophages in nearly all experimental cases were downregulated and not significantly different from those of the operative controls (p > 0.05). The spinal cord had no evidence of lesions or neuropathology. However, multiple treatments in the metallic groups exhibited a mild, chronic macrophage response to particulate debris, which had diffused intrathecally. Epidural application of spinal instrumentation particulate wear debris elicits a chronic histiocytic reaction localized primarily within the epidural fibrosis. Particles have the capacity to diffuse intrathecally, eliciting a transient upregulation in macrophage/cytokine activity response within the epidural fibrosis. Overall, based on the time periods evaluated, there was no evidence of an acute neural or systemic histopathological response to the materials included in the current project.

Total Knee Prosthesis Polyethylene wear Reduction by a New Metal Part Finishing Method

The purpose of this study was to assess a new metal component finishing designed to improve total knee prosthesis durability. Wear of ultrahigh molecular-weight polyethylene (UHMWPE), with generation of submicrometer- and micrometer-sized particles, has been associated with osteolysis and artificial joint failure. Wear extent is influenced by several factors, some of which are related to manufacturing. UHMWPE wear was assessed in metal prosthesis components finished with the Microloy® technology and in traditionally finished components by wear simulation experiments (pin on disk and knee simulator tests) and analysis of wear debris. Microloy®-finished prosthesis showed a 48.5% reduction in UHMWPE total weight loss compared with traditional components (P=0.002). A statistically significant (P<0.05) reduction of UHMWPE debris were detected from the Microloy®-finished compared with the traditionally finished components. These findings suggest the Microloy® metal finishing may enhance the long-term performance of knee prostheses.

Deposition of a-C:H films on UHMWPE substrate and its wear-resistance

In prosthetic hip replacements, ultrahigh molecular weight polyethylene (UHMWPE) wear debris is identified as the main factor limiting the lifetime of the artificial joints. Especially UHMWPE debris from the joint can induce tissue reactions and bone resorption that may lead to the joint loosening. The diamond like carbon (DLC) film has attracted a great deal of interest in recent years mainly because of its excellent tribological property, biocompatibility and chemically inert property. In order to improve the wear-resistance of UHMWPE, a-C:H films were deposited on UHMWPE substrate by electron cyclotron resonance microwave plasma chemical vapor deposition (ECR-PECVD) technology. During deposition, the working gases were argon and acetylene, the microwave power was set to 800 W, the biased pulsed voltage was set to −200 V (frequency 15 kHz, duty ratio 20%), the pressure in vacuum chamber was set to 0.5 Pa, and the process time was 60 min. The films were analysed by X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, nano-indentation, anti-scratch and wear test. The results showed that a typical amorphous hydrogenated carbon (a-C:H) film was successfully deposited on UHMWPE with thickness up to 2 μm. The nano-hardness of the UHMWPE coated with a-C:H films, measured at an applied load of 200 μN, was increased from 10 MPa (untreated UHMWPE) to 139 MPa. The wear test was carried out using a ball (Ø 6 mm, SiC) on disk tribometer with an applied load of 1 N for 10000 cycles, and the results showed a reduction of worn cross-sectional area from 193 μm 2 of untreated UHMWPE to 26 μm 2 of DLC coated sample. In addition the influence of argon/acetylene gas flow ratio on the growth of a-C:H films was studied.

Effect of submicron polyethylene particles on an osseointegrated implant: an experimental study with a rabbit patello-femoral prosthesis.

In a rabbit model of a weight bearing, articulating prosthetic joint we repeatedly injected submicron particles of Ultra-High-Molecular-Weight-Polyethylene (UHMWPE) produced in a hip simulator. The contralateral knee with the same prosthesis was injected with carrier (NaCl) without UHMWPE. Histomorphometrical studies on undecalcified cut and ground sections at 26 and 42 weeks involved quantifications of the entire bone to metal contact and the bone area around each implant. We found no statistically significant differences between test and control groups, and the UHMWPE debris did not induce any significant osteolysis, indicating that an osseointegrated implant with a sealed interface may not be affected by UHMWPE debris or progress to aseptic loosening.

Failure of a metal-on-metal total hip arthroplasty from progressive osteolysis

Ultra-high-molecular weight polyethylene (UHMWPE) wear, debris-induced osteolysis is a frequent cause of failure of total hip arthroplasty. Metal-on-metal total hip arthroplasty eliminates the generation of UHMWPE particulate debris. Although the volumetric wear of a metal-on-metal articulation may be lower than a metal-UHMWPE articulation, the number of particles may be higher. Osteolysis can develop in response to metallic and UHMWPE debris. The following case of massive osteolysis associated with large amounts of cobalt-chrome wear debris shows adhesive and abrasive wear mechanisms, as well as wear caused by third-body cobalt-chrome debris and impingement of the femoral component against the rim of the acetabular cup, which led to failure of a metal-on-metal total hip arthroplasty.

Bisphosphonate therapy for the prevention of osteolysis in total joint replacements

Aseptic loosening is the number one impediment to extending the useful life span of total joint replacements. The etiologic agent is believed to be submicron ultrahigh molecular weight polyethylene debris from the acetabular liner, which stimulates a macrophage-mediated inflammatory response. Therapeutic approaches using bisphosphonates represent a convenient and effective manner to target the end effector cell, which is the osteoclast. The studies reviewed here highlight the encouraging prospects of using bisphosphonates to prevent and potentially treat periprosthetic bone loss associated with osteolysis. There appear to be minimal complications, and the mechanisms of action are fairly well understood. Thus, bisphosphonates are appropriate candidates in a growing repertoire of materials development, implant design, and pharmaceutical agents to combat periprosthetic osteolysis.