The influence of polyimide MP-1™ wear particles on a rodent closed fracture healing model.

Joint replacements provide pain free movement for the injured or our aging population. Current prothesis mainly consist of hard metal on metal, or ceramic femoral head on ultra-high-molecular weight polyethylene (UHMWPE). In this study, a rodent fracture model was used to test the influence of wear debris from a high-performance polymer (polyimide MP-1™). Saline, MP-1™ Low Dose in Saline (1%), or MP-1 High Dose (2%) in Saline was injected directly into a standard closed unilateral femoral fracture in 12-week old Sprague Dawley rats (n = 25) for 1, 3 and 6 weeks. Endpoints included radiography, micro-computed tomography, mechanical testing and paraffin histology. No adverse effects from the wear particles were observed from the current study based on radiology, mechanical or histological data. Although the particles were present, histological analysis revealed a progression in healing between the Polyimide treated groups and the non-treated saline control groups over the duration of 1, 3, and 6 weeks, with no inhibition from the particles. The MP-1™ wear debris generated are larger than 1 µm thus are not able to be engulfed by macrophages and cause osteolysis. This family of polymers (polyimides) may be an ideal material to consider for articulating joints and other implants in the human body.

Clearance of senescent cells by navitoclax (ABT263) rejuvenates UHMWPE-induced osteolysis.

Periprosthetic osteolysis is the leading cause of prosthesis failure and subsequent total joint revision. Wear particles produced by prosthetic materials are the main biological factors that cause periprosthetic osteolysis. Reducing the inflammatory response induced by the phagocytosis of wear particles by macrophages, blocking the activation of osteoclastogenesis, and promoting bone regeneration are essential for preventing the aseptic loosening of prostheses. In this study, we demonstrated that cellular senescence played a vital role during the process of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. Administration of the senolytic drug navitoclax (ABT263) could eliminate senescent cells and inhibit the secretion and inflammatory state of the senescence-associated secretory phenotype (SASP). We also discovered that ABT263 inhibited the formation of osteoclasts and had a significant therapeutic effect on UHMWPE particle-induced osteolysis based on the results of UHMWPE-induced mouse cranial osteolysis. Therefore, our research provided innovative strategies and ideas for the prevention and treatment of periprosthetic osteolysis.

Ear Reconstruction with the Combination of Expanded Skin Flap and Medpor Framework: 20 Years of Experience in a Single Center.

BACKGROUND: In ear reconstruction, the difficulty lies in reestablishing the ear's bionic form with adequate skin coverage and an appropriate framework. Skin expansion and a porous polyethylene (i.e., Medpor) framework are often used for ear reconstruction. However, a long-term review of the combined application of the expanded skin and Medpor framework has not been reported. This article reviews ear reconstruction combining these two factors over the past 20 years in the authors' center to summarize the surgical technique and analyze the postoperative results and complications. METHODS: A retrospective review was performed that included all patients who underwent ear reconstruction with expanded skin and Medpor framework in the authors' center between 1998 and 2018. RESULTS: A total of 68 patients with microtia who were admitted to the authors' center for surgical ear reconstruction were included, and 70 ears were reconstructed. Fifty-seven of the patients (83.82 percent) felt satisfied with their reconstructed ear, five patients (7.35 percent) were not satisfied with the reconstructed ear, and six patients (8.82 percent) had the frameworks removed. Fifteen patients (22.06 percent) developed complications, including framework exposure (13.24 percent), infection (4.41 percent), scar hypertrophy (4.41 percent), and hematoma (2.94 percent). CONCLUSIONS: Framework exposure limits the combined application of expanded skin flap and Medpor framework when reconstructing the ear without additional fascial interposition. Using a temporoparietal fascia or postauricular fascia flap during the operation is effective to decrease the exposure rate; however, this complication cannot be completely avoided. Using postauricular fascia and skin graft may lead to scar hypertrophy; thus, these techniques should be used with caution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Septorhinoplasty for Destructed Septal L-Strut in Patients with Previously Applied Porous High-Density Polyethylene Implants (Medpor®).

BACKGROUND: Porous high-density polyethylene implants (Medpor®) have been extensively used for septal extension grafts in Asian rhinoplasty. However, studies on the long-term complications associated with Medpor® have not been reported. Therefore, the purpose of this study was to evaluate the long-term complications of septal extension grafts using Medpor® and present a reconstructive strategy for destructed septal L-struts. METHODS: We conducted a 12-year retrospective medical chart review of 428 patients who visited our center for septorhinoplasty. Among 428 patients, 43 patients had Medpor® for septal extension grafts previously applied at other clinics. The quadrangular cartilage was devoid or destructed in the area where Medpor® was previously applied. Therefore, all patients underwent secondary septorhinoplasty using autogenous cartilage grafts. Patient outcome was assessed to evaluate satisfaction, hardness of nasal tip, functional nasal obstruction symptom evaluation (NOSE) scores, and pain scores. Anthropometric analyses were carried out with patients' photographs. Postoperative complications were also evaluated. RESULTS: After septal L-strut reconstruction, 87% of patients were satisfied with their aesthetic results. Hardness of nasal tip, NOSE scores, and pain scores also improved after reconstruction. Anthropometric analyses demonstrated that increased nasal length and decreased columellar-labial angle were achieved in patients with short nose deformities. No postoperative complications related to the reconstruction were recorded for any patient. CONCLUSIONS: The devastated destruction of nasal support lines was found after the use of Medpor® for septorhinoplasty. Therefore, the use of Medpor® should be reduced. Autogenous cartilage grafts are the last resort for reconstruction of destructed septal L-struts. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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 SIGNIFICANCE: Aseptic 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.

Osteocytes respond to particles of clinically-relevant conventional and cross-linked polyethylene and metal alloys by up-regulation of resorptive and inflammatory pathways.

Periprosthetic osteolysis is a major cause of implant failure in total hip replacements. Aseptic loosening caused by osteolytic lesions is associated with the production of bioactive wear particles from the articulations of implants. Wear particles infiltrate the surrounding tissue of implants, promoting inflammation as well as bone resorption. Osteocytes have been shown to both regulate physiological osteoclastogenesis and directly remodel their perilacunar bone matrix by the process of osteocytic osteolysis. We hypothesise that osteocytes respond to wear debris of orthopaedic implant materials by adopting a pro-catabolic phenotype and thus contribute to periprosthetic osteolysis through the known pathways of bone loss. Osteocyte responses to particles derived from clinically relevant materials, ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE) and metal alloys, Ti6Al4V and CoCrMo, were examined in vitro in human primary osteocyte-like cultures. Osteocyte-like cells exposed to both polyethylene and metal wear particle types showed upregulated expression of catabolic markers associated with osteocytic osteolysis, MMP13, carbonic anhydrase 2 (CA2) and cathepsin K (CTSK). In addition, pro-osteoclastogenesis markers RANKL and M-CSF were induced, as well as the expression of pro-inflammatory cytokines, IL-6 and TNFα, albeit with different kinetics. These findings suggest a previously unrecognised action of wear particles of multiple orthopaedic materials on osteocytes, and suggest a multifaceted role for osteocytes in periprosthetic osteolysis. STATEMENT OF SIGNIFICANCE: This study addresses periprosthetic osteolysis, a major clinical problem leading to aseptic loosening of orthopaedic implants. It is well accepted that wear particles of polyethylene and of other implant materials stimulate the activity of bone resorbing osteoclasts. Our recent work provided evidence that commercial particles of ultra-high molecular weight polyethylene (UHMWPE) stimulated osteocytes to adopt a bone catabolic state. In this study we demonstrate for the first time that particles derived from materials in clinical use, conventional UHMWPE, highly cross-linked polyethylene (XLPE), and Ti6Al4V and CoCrMo metal alloys, all stimulate human osteocyte activities of osteocyte-regulated osteoclastogenesis, osteocytic osteolysis, proinflammatory responses, osteocyte apoptosis, albeit to varying extents. This study provides further mechanistic insight into orthopaedic wear particle mediated bone disease in terms of the osteocyte, the most abundant and key controlling cell type in bone.

[Comparison of Explanted UHMWPE Hip Replacement Components of Various Manufacturers after 10 Years in vivo]. / Porovnání explantovaných UHMWPE komponent náhrady kycelního kloubu ruzných výrobcu po 10 letech in vivo.

PURPOSE OF THE STUDY Considered to be one of the most common causes of aseptic loosening of endoprostheses is the THA failure due to the wear of articulating components, UHMWPE in particular. The purpose of this study is to verify, in terms of oxidative damage and other parameters, the differences between the UHMWPE implants made by various manufacturers explanted for aseptic loosening with the same life span in vivo. MATERIAL AND METHODS In the period 2010-2015, a total of 21 THA articulating components (cups) made of Ultrahigh molecular weight polyethylene by seven different manufacturers were explanted. For each manufacturer, three UHMWPE cups with the same life span (10-12 years after the primary implantation) were evaluated. The damage to the examined joint replacements was described in complexity using three different criteria, namely independently by three evaluators - experienced orthopaedic surgeons. The evaluated criteria were the following: degree of osteolysis determined based on the preoperative radiographs, wear rate of the explanted UHMWPE component, and extent of perioperatively detected granuloma. Oxidative damage and other structural characteristics of explanted cups were studied by means of infrared spectroscopy and microhardness testing. The correlation between the clinical orthopaedic assessment and oxidative damage were statistically processed. RESULTS Strong correlations between the oxidative damage and crystallinity, strong correlations between all types of orthopaedic assessments, negligible correlations between trans-vinylene index and all the other quantities, and moderate correlations between the oxidative damage and clinical evaluation were identified. It was confirmed by experimental measurement that the observed high oxidative damage, resulting in increased crystallinity, manifested itself also in micromechanical properties of the material at the respective site of the THA articulating component. DISCUSSION The discussion includes the comparison of correlations of individual quantities as well as potential effects on the differences in values of components made by individual manufacturers. The values are related to the data in literature and generally accepted claims. CONCLUSIONS At the time of failure almost all the components showed severe or even critical oxidative damage that strongly correlated with the overall clinical evaluation of the damage to the implant. This confirmed that the oxidative degradation is one of the main causes of THA failure. Key words: UHMWPE, oxidation index, crystallinity, THA failure, wear.

[The Risk of Total Joint Replacement Infectious Complications in Relation to the UHMWPE Particle Adhesion Area]. / Riziko infekcních komplikací po náhrade nosného kloubu ve vztahu k adhezní plose UHMWPE cástic.

PURPOSE OF THE STUDY Periprosthetic joint infection is a major complication which in most of the cases requires a long-term administration of antibiotics and often necessitates undergoing multiple challenging surgeries. Bacterial adhesion to foreign material is one of the key risk factors associated with periprosthetic joint infection. The foreign material with large adhesion area might be also the UHMWPE (Ultrahigh molecular weight polyethylene) particles released during the wear process from the surface of articulating components. The purpose of this study is to evaluate potential adhesion areas of wear particles in relation to diverse distribution of the size and shapes of wear particles in periprosthetic tissue and to assess an increase in the risk of infectious complications associated with an increase in the adhesion area of wear particles. MATERIAL AND METHODS The size and morphology of model and real UHMWPE particles were determined with the use of light microscopy and scanning electron microscopy. By determining the morphological descriptors, the surfaces of individual particles for different distributions of polyethylene particles were calculated. When measuring the model wear particles, 6 model situations were simulated, in which comparisons with the control measurement by the BET (Brunauer-Emmet-Teller) method were made. RESULTS The variability of individual morphological descriptors demonstrates the effect on the total surface of particles. The calculated coefficient defines how many times the particle surface increases when corrected to the given descriptor (elongation, flattening, roughness, porosity). The total area of real wear particles at 1 year is 4,622 cm2, at 20 years it is 92,440 cm2. Based on our calculations, the area of particles where a biofilm is actually formed (approximately 50 bacteria may adhere to a particle of 3µm in diameter) is 809.5 cm2 at 1 year and 16,190 cm2 at 20 years. DISCUSSION According to the measurements, the size of the potential adhesion area of metal parts and polyethylene particles becomes equal already after several weeks of endoprosthesis usage and after a few years it is many times larger. The question is whether the risk of bacterial adhesion, i.e. also the risk of infectious complications of TEP actually increases. The clinical practice suggests that the number of infections e.g. 10, 15 or 20 years after the primary implantation is not statistically higher, despite the confirmed growth of potential adhesion area in the form of UHMWPE particles. This fact could be explained by a partially equal regulatory pathway of infection and polyethylene disease. The immune system stimulated by wear particles might better resist the hematogenic infection. CONCLUSIONS The study outcomes clearly indicate that the area of polyethylene wear particles considerably increases over time. In spite of the fact that only approximately 10% of wear particles show parameters (also with respect to the size of particles and bacteria) for potential bacterial adhesion, this area is many times larger than the area of metal parts of the endoprosthesis. Key words: UHMWPE particle, adhesion, biofilm, wear, TJR infection.

Effects of vitamin E incorporation in polyethylene on oxidative degradation, wear rates, immune response, and infections in total joint arthroplasty: a review of the current literature.

Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) was introduced to decrease wear debris and osteolysis. During cross-linking, free radicals are formed, making highly cross-linked polyethylene vulnerable to oxidative degradation. In order to reduce this process, anti-oxidant vitamin E can be incorporated in polyethylene. This review provides an overview of the effects of vitamin E incorporation on major complications in total joint arthroplasty: material failure due to oxidative degradation, wear debris and subsequent periprosthetic osteolysis, and prosthetic joint infections. Secondly, this review summarizes the first clinical results of total hip and knee arthroplasties with vitamin E incorporated highly cross-linked polyethylene. Based on in vitro studies, incorporation of vitamin E in polyethylene provides good oxidative protection and preserves low wear rates. Incorporation of vitamin E may have the beneficial effect of reduced inflammatory response to its wear particles. Some microorganisms showed reduced adherence to vitamin E-incorporated UHMWPE; however, clinical relevance is doubtful. Short-term clinical studies of total hip and knee arthroplasties with vitamin E-incorporated highly cross-linked UHMWPE reported good clinical results and wear rates similar to highly cross-linked UHMWPE without vitamin E.

Metformin protects bone mass in ultra-high-molecular-weight polyethylene particle-induced osteolysis by regulating osteocyte secretion.

Metformin, an anti-hyperglycemic agent used for type 2 diabetes, has recently been found to have more effects apart from glucose regulation. We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-κB Ligand (RANKL). In vitro, we established a 3D co-culture system in which metformin affects osteoblasts and osteoclasts through mature osteocytes secretion. Metformin (50 µM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis. Moreover, the effect on OPG was reversed by adenosine 5'-monophosphate-activated protein kinase inhibitor, Compound C. Our finding suggests that metformin induces differentiation and mineralization of osteoblasts, while inhibits osteoclastogenesis via mature osteocytes secretion. Therefore, the drug might be beneficial for not only diabetes but also in other bone disorders by acting on mature osteocytes.

Peristomal allergic contact dermatitis caused by ostoma pastes and role of Gantrez ES-425.

BACKGROUND: Peristomal allergic contact dermatitis is an emerging problem and contact sensitization is probably more common than previously thought. Our objective was to identify sensitization to the most common topical equipment for ostomy in patients with history of peristomal dermatitis. METHODS: Twenty-six patients with suspected peristomal contact dermatitis were patch tested with our standard series and with products for stoma care (adhesive pastes, powders, adhesive skin barriers). Thirteen patients and 20 volunteers were also patch tested with Gantrez ES-425, which is a common component of adhesive pastes. RESULTS: Eighteen patients showed one or more positive reactions, 12 to one or more of the most commonly used adhesive pastes. Ten out of 13 patients tested to Gantrez ES-425 had a positive reaction. CONCLUSIONS: Allergic contact dermatitis of the peristomal area is probably more common than previously reported. Patch testing is the method of choice to determine sensitization to products for stoma care, and Gantrez ES-425 should be considered for patch testing.

The Role of IL-6RA in UHMWPE Promotes Proliferation in Fibro-Like Synovial Cells.

UHMWPE granule could induce macrophages and inflammatory responses in interfacial tissues, which eliminated the wear debris of UHMWPE component and further induced dissolution of the surrounding bone, leading aseptic loosening. However, the mechanism of synovial cells, especially fibroblast-like synovial (FLS) cells response to UHMWPE, remains unknown. Herein we choose FLS cells as research object. Vimentin (+) CD68 (-) was identified by flow cytometry and immunofluorescent staining assay, and the cells were identified as FLS cells, which was consistent with the experimental requirements. The inhibitory evaluation showed that UHMWPE could significantly promote the proliferation and inhibit apoptosis of FLS cells in dose- and time-dependent manners and increase the levels of proinflammatory cytokines, including IL-6, IL-1ß, TNF-α, PGE2, MMP2, and LOX. UHMWPE also can induce the expression of mIL-6R protein in FLS cells and further investigate the relationship between apoptosis and inflammation. Interestingly enough, when we added the interleukin-6 receptor antagonist (IL-6RA), the expression levels of proapoptosis-related proteins increased; in other words, UHMWPE-induced antiapoptosis diminished by IL-6RA (50 µg/ml). Taken together, these findings clearly demonstrated that UHMWPE promote growth in FLS cells through upregulating inflammatory factors to produce antiapoptotic effect.

NFκB sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles.

Total joint replacement is a highly effective treatment for patients with end-stage arthritis. Proinflammatory macrophages (M1) mediate wear particle-associated inflammation and bone loss. Anti-inflammatory macrophages (M2) help resolve tissue damage and favor bone regeneration. Mesenchymal stem cell (MSC)-based therapy mitigates the M1 dominated inflammatory reaction and favorably modulates the bone remodeling process. In the current study, the immunomodulating ability of (1) unmodified MSCs, (2) MSCs preconditioned by NFκB stimulating ligands [lipopolysaccharide (LPS) plus TNFα], and (3) genetically modified MSCs that secrete IL-4 as a response to NFκB activation (NFκB-IL4) was compared in a macrophage/MSC co-culture system. Sterile or LPS-contaminated ultra-high molecular weight polyethylene particles were used to induce the proinflammatory responses in the macrophages. Contaminated particles induced M1 marker expression (TNFα, IL1ß, and iNOS), while NFκB-IL4 MSCs modulated the macrophages from an M1 phenotype into a more favorable M2 phenotype (Arginase 1/Arg 1 and CD206 high). The IL4 secretion by NFκB-IL4 MSCs was significantly induced by the contaminated particles. The induction of Arg 1 and CD206 in macrophages via the preconditioned or naïve MSCs was negligible when compared with NFκB-IL4 MSC. Our findings indicated that NFκB-IL4 MSCs have the "on-demand" immunomodulatory ability to mitigate wear particle-associated inflammation with minimal adverse effects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2744-2752, 2018.

Immunobiology of periprosthetic inflammation and pain following ultra-high-molecular-weight-polyethylene wear debris in the lumbar spine.

INTRODUCTION: Wear debris-induced osteolysis is a common cause of arthroplasty failure in several joints including the knee, hip and intervertebral disc. Debris from the prosthesis can trigger an inflammatory response that leads to aseptic loosening and prosthesis failure. In the spine, periprosthetic pain also occurs following accumulation of wear debris through neovascularization of the disc. The role of the immune system in the pathobiology of periprosthetic osteolysis of joint replacements is debatable. Areas covered: We discussed the stimulation of pro-inflammatory and pro-protective and pro-regenerative pathways due to debris from the prosthetics. The balance between the two pathways may determine the outcome results. Also, the role of cytokines and immune cells in periprosthetic inflammation in the etiology of osteolysis is critically reviewed. Expert commentary: Therapies targeting the inflammatory process associated with ultra-high-molecular-weight polyethylene wear debris could reduce implant failure. Additionally, therapies targeting neovascularization of discs following arthroplasty could mitigate periprosthetic pain.

Causes of the Removal of High-Density Polyethylene Sheets (Medpor) in Revision Rhinoplasty.

The aim of this study was to identify the causes of complications in rhinoplasties using Medpor. The medical records of 71 patients who had undergoing a reoperation after a rhinoplasty using Medpor were reviewed. From each patient's history, examination records, and operative records, the method of the previous rhinoplasty using Medpor was extracted. The previously inserted Medpor and the septal mucosa covering it were removed during the reoperation and observed in 3 cases. A turned-up or short nose (43.8%) and tip stiffness (25.3%) were significantly more common than other complaints (P < 0.05). The strut type (49.2%) and the septal extension type (43.8%) were significantly more common than the spreader type (P < 0.001). In the reoperation, extension grafts (47.1%) and by tip grafts (39.7%) were significantly more common than other procedures (P < 0.001). Grossly, the specimens were covered with septal mucosa and multiple ball-like granulation tissues (cobblestone appearance) at the "pores" of the Medpor. Microscopically, Medpor was covered with fibrous collagenous tissue, partially bridging through the pores. Inflammatory cells had infiltrated around the polyethylene. The authors classify the patients in the present series as: those with a long columella strut to the anterior nasal spine, those with Medpor inserted onto the membranous septum (septal extension graft or too large), and those with Medpor used as spreader graft covered with nasal mucosa (causing weakness of the nasal septum and thinning or necrosis of the mucosa). Using Medpor as a strut graft seems to be relatively safe if the floating type is used.

* Murine Model of Progressive Orthopedic Wear Particle-Induced Chronic Inflammation and Osteolysis.

Periprosthetic osteolysis and subsequent aseptic loosening of total joint replacements are driven by byproducts of wear released from the implant. Wear particles cause macrophage-mediated inflammation that culminates with periprosthetic bone loss. Most current animal models of particle-induced osteolysis are based on the acute inflammatory reaction induced by wear debris, which is distinct from the slowly progressive clinical scenario. To address this limitation, we previously developed a murine model of periprosthetic osteolysis that is based on slow continuous delivery of wear particles into the murine distal femur over a period of 4 weeks. The particle delivery was accomplished by using subcutaneously implanted osmotic pumps and tubing, and a hollow titanium rod press-fit into the distal femur. In this study, we report a modification of our prior model in which particle delivery is extended to 8 weeks to better mimic the progressive development of periprosthetic osteolysis and allow the assessment of interventions in a setting where the chronic particle-induced osteolysis is already present at the initiation of the treatment. Compared to 4-week samples, extending the particle delivery to 8 weeks significantly exacerbated the local bone loss observed with µCT and the amount of both peri-implant F4/80+ macrophages and tartrate-resistant acid phosphatase-positive osteoclasts detected with immunohistochemical and histochemical staining. Furthermore, systemic recruitment of reporter macrophages to peri-implant tissues observed with bioluminescence imaging continued even at the later stages of particle-induced inflammation. This modified model system could provide new insights into the mechanisms of chronic inflammatory bone loss and be particularly useful in assessing the efficacy of treatments in a setting that resembles the clinical scenario of developing periprosthetic osteolysis more closely than currently existing model systems.

Effects of vitamin E-diffused highly cross-linked UHMWPE particles on inflammation, apoptosis and immune response against S. aureus.

Particle-induced osteolysis and periprosthetic joint infection (PJI) are closely associated with periprosthetic tissue immune function. The objective of this study was to determine the effects of polyethylene particles on inflammation and response against S. aureus. Effects that vitamin E-diffused cross-linked UHMWPE (VE-PE) particles had on apoptosis, inflammation, and bactericidal activities compared to virgin cross-linked UHMWPE (control PE) particles were examined. Murine RAW 264.7 macrophages exposed to VE-PE particles in vitro were less apoptotic, secreted less tumor necrosis factor (TNF)-α, and responded more effectively against lipopolysaccharide or S. aureus compared to control PE particles. Implantation of VE-PE particles in murine calvaria in vivo caused less reactive oxygen species generation, less apoptosis, and less osteolysis compared to control PE particles. Implantation of PE particles in mice calvaria for 28 days, followed by inoculation with S. aureus in the same site where PE particles were implanted, demonstrated enhanced S. aureus clearance in the VE-PE group at day 33 after inoculation. These findings indicate that VE-PE particles might be less inflammatory and might preserve innate immunity of local tissue, allowing for enhanced clearance of bacteria.

The Relationship Between Polyethylene Wear and Periprosthetic Osteolysis in Total Hip Arthroplasty at 12 Years in a Randomized Controlled Trial Cohort.

BACKGROUND: Polyethylene acetabular components are common in hip arthroplasty. Highly cross-linked polyethylene (HXLPE) has lower wear than ultra-high molecular weight polyethylene (UHMWPE). Evidence suggests that wear particles induce inflammation causing periprosthetic osteolysis contributing to implant loosening with wear rates of 0.05 mm/y were considered safe. We aimed to compare incidence and volume of periacetabular osteolysis between HXLPE and UHMWPE using computed tomography. METHODS: Initially, 54 hips in 53 patients were randomized to HXLPE or UHMWPE acetabular liner. At 10 years, 39 hips in 38 patients remained for the radiostereometric analysis' demonstrating significantly lower wear in the HXLPE group. At 12 years, 14 hips in 13 patients were lost to follow-up leaving 25 hips for computed tomography assessment. Images were reconstructed to detect osteolysis and where identified, areas were segmented and volumized. RESULTS: Osteolysis was observed in 8 patients, 7 from the UHMWPE group and only 1 from the HXLPE group (Fisher exact, P = .042). There was no correlation between the amount of polyethylene wear and osteolysis volume; however, the radiostereometric analysis-measured wear rate in patients with osteolysis from both groups was significantly higher than overall average wear rate. CONCLUSION: This data demonstrates lower incidence of periacetabular osteolysis in the HXLPE group of a small cohort. Although numbers are too low to estimate causation, in the context of lower wear in the HXLPE group, this finding supports the hypothesis that HXLPE may not elevate osteolysis risk, and hence does not suggest that HXLPE wear particles are more biologically active than those generated by earlier generations of polyethylene.

Highly crosslinked polyethylene: a safe alternative to conventional polyethylene for dual mobility cup mobile component. A biomechanical validation.

PURPOSE: Dual mobility cup (DMC) consists of a cobalt-chromium (CoCr) alloy cup articulated with a polyethylene (PE) mobile component capturing the femoral head in force using a snap-fit technique. This biomechanical study was the first to evaluate and compare the generation of cracks in the retentive area of DMC mobile components made of highly crosslinked PE (XLPE) or conventional ultra-high molecular weight PE (UHMWPE). METHODS: Eighty mobile components designed for a 52-mm diameter Symbol® DMC (Dedienne Santé, Mauguio, France) and a 28-mm diameter femoral head were analyzed. Four groups of 20 mobile components were constituted according to the PE material: raw UHMWPE, sterilized UHMWPE, annealed XLPE and remelted XLPE. Ten mobile components in each group were impacted with a 28-mm diameter CoCr femoral head using a snap-fit technique. The occurrence, location and area of the cracks in the retentive area were investigated using micro-CT (Skyscan 1176®, Bruker, Aarsellar, Belgium) with a 35 µm nominal isotropic voxel size by two observers blinded to the PE material and impaction or not of the mobile components. RESULTS: Compared to conventional UHMWPE, the femoral head snap-fit did not generate more or wider cracks in the retentive area of annealed or remelted XLPE mobile components. CONCLUSION: This biomechanical study suggests that XLPE in DMC could be a safe alternative to conventional UHMWPE regarding the generation of cracks in the retentive area related to the femoral head snap-fit.

Equivalent wear performance of dual mobility bearing compared with standard bearing in total hip arthroplasty: in vitro study.

PURPOSE: Osteolysis in total hip arthroplasty (THA) depends on polyethylene wear and dictates the survival of the prosthesis. Dual mobility in THAs, which is claimed to reduce dislocation risk, has very good long-term clinical results. However, little is known about how the liner wears in this design, compared to the standard single mobility model. METHODS: A comparative study looking at wear of a conventional ultra-high-molecular-weight polyethylene liner, using gravimetric measurement, between dual mobility implants and standard implants, was performed on a simulator in accordance with a normed protocol based on the same dimensions, environmental conditions and stresses. A linear regression test was employed. RESULTS: Under the same conditions (loading, cycles, sterilization, material and surface roughness), the gravimetric wear (for conventional polyethylene) is comparable between a standard and a dual mobility cup. This correlates to ten year follow-up results of dual mobility cup. DISCUSSION - CONCLUSION: This in vitro equivalent wear serves to confirm the very good long-term clinical results observed with dual mobility bearing, whose use should not be restricted by concerns about increased polyethylene wear.