Introduction. The combined incidence of anatomic (aTSA) and reverse total shoulder arthroplasties (rTSA) in the US is 90,000 per annum and rising. There has been little attention given to potential long-term complications due to periprosthetic tissue reactions to implant debris. The shoulder has been felt to be relatively immune to these complications due to lower acting loads compared to other joint arthroplasties. In this study, retrieved aTSAs and rTSAs were examined to determine the extent of implant damage and to characterize the nature of the corresponding periprosthetic tissue responses. Methods. TSA components and periprosthetic tissues were retrieved from 23 (eleven aTSA, twelve rTSA). Damage to the implants was characterized using light microscopy. Head/stem taper junction damage was graded 1–4 as minimal, mild, moderate or marked. Damage on polyethylene (PE) and metal bearing surfaces was graded 1–3 (mild, moderate, marked). H&E stained sections of periprosthetic soft tissues were evaluated for the extent and type of cellular response. A semi-quantitative system was used to score (1=rare to 4=marked) the overall number of particle-laden
It has been previously shown that Low-Magnitude High-Frequency Vibration (LMHFV) is able to enhance ovariectomy-induced osteoporotic fracture healing in rats. Fracture healing begins with the inflammatory stage, and all subsequent stages are regulated by the infiltration of immune cells such as
It is reported that more than 10 million Japanese suffer from arthrosis. To cure these cartilage defects, total joint replacements, which are the most popular treatment methods for severe disease situation, have been operated as about two hundred thousand cases a year in Japan. Although the implants made of either ceramics, metals or plastics have high wear resistance quality, it becomes apparent that the endurance life of the artificial joints in considerable cases is limited by aseptic loosening to between 10–15 years. Here we focused on a poly(vinyl alcohol) (PVA) hydrogel as an artificial cartilage tissue to make an improvement of friction surface of the artificial joints. In this paper, we observed morphology of wear particles and assessed immune responses of wear particles from the hydrogel for confirming the validity of the gel as a biotribological material. We prepared 20 w/w% of PVA hydrogel by repeated freezing-thawing method. The number of the freezing-thawing cycles was five times. Polymerization degree and saponification degree of PVA (Kishida Chemical Co. Ltd., Japan) were 2000 and 98.4–99.8 mol%, respectively. To collect the wear particles of PVA hydrogel, we processed wear testing by using a purpose-build wear test machine of reciprocating pin-on-plate tribometer as shown in figure 1. We installed a Co-Cr-Mo ball of 26 mm in diameter as a stationary upper specimen and a PVA hydrogel plate of 2 mm in thickness as reciprocating lower specimen in a water bath. The lubricant was a distilled water containing eluted PVA which PVA-FT gel had been soaked in, filtered by 0.22 μm and autoclaved, subsequently. Siding speed was 50 mm/s and the total sliding distance was 3 km. We observed the wear particles which had been dried in a desiccator, by scanning electron microscope (SEM; SU8000, Hitachi High-Technologies). Additionally, to investigate the effect of the wear particles on response of phagocytosis of
Introduction. Periprosthetic joint infection (PJI) and particle-induced osteolysis are closely related to peri-implant local immunity and
Aims. This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear
This study presents the use of precision surface machining on artificial joint bearing surfaces in order to inhibit
An ultra-high molecular weight polyethylene (UHMWPE) is widely used as bearing material in artificial joints, however, UHMWPE wear particles are considered to be a major factor in long-term osteolysis and loosening of implants. The wear particles activate
An ultra-high molecular weight polyethylene (UHMWPE) is widely used as bearing material in artificial joints, however, UHMWPE wear particles are considered to be a major factor in long-term osteolysis and loosening of implants. The wear particles activate
Aim. In the current study we aim to characterize the use of cationic host defense peptides (HDPs) as alternative antibacterial agents to include into novel antibacterial coatings for orthopedic implants. Staphyloccous aureus represent one the most challenging cause of infections to treat by traditional antibacterial therapies. Thanks to their lack of microbial resistance described so far, HDPs represent an attractive therapeutic alternative to antibiotics. Furthermore, HDPs have been showed to control infections via a dual function: direct antimicrobial activity and regulation of immune response. However, HDPs functions characterization and comparison is controversial, as changing test conditions or cell type used might yield different effects from the same peptide. Therefore, before moving towards the development of HDP-based coatings, we need to characterize and compare the immunomodulatory and antibacterial functions under the same conditions in vitro of 3 well-known cathelicidins: human LL-37, chicken CATH-2, and bovine-derived IDR-1018. Method. S. aureus, strain SH1000, was incubated with different concentrations of each HDP and bacterial growth was monitored overnight. Primary human monocytes were isolated from buffy coats using Ficoll-Paque density and CD14 microbeads, and differentiated for 7 days to
Aim. Staphylococcus aureus (SA) can cause various infections and is associated with high morbidity and mortality rates of up to 40%. Antibiotic treatment often fails to eradicate SA infections even if the causative strain has been tested susceptible in vitro. The mechanisms leading to this persistence is still largely unknown. In our work, we to reveal SA interactions with host cells that allow SA to persist at the site of infection. Method. We established a sampling workflow to receive tissue samples from patients requiring surgical debridement due to SA bone-and joint or soft-tissue infections. We developed a multiplex immunofluorescent staining protocol which allowed us to stain for SA, leukocytes, neutrophils,
Mesenchymal stem cells (MSCs) are capable of forming bone, cartilage and other mesenchymal tissues but are also important modulators of innate and adaptive immune responses. We have capitalized on these important functions to mitigate adverse responses when bone is exposed to pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), or prolonged pro-inflammatory cytokines. Our goal was to optimize osteogenesis and mitigate persistent undesired inflammation by: 1. preconditioning MSCs by short term exposure to lipopolysaccharide (LPS) and Tumor Necrosis Factor alpha (TNF-α), 2. genetic modification of MSCs to overexpress Interleukin 4 (IL-4) either constitutively, or as NFκB-responsive IL-4 over-expression cells, and 3. training the MSCs (innate immune memory) by repeated stimulation with LPS. In the first experiment, bone marrow MSCs and
Wear and corrosion debris generated from total hip replacements (THR) can cause adverse local tissue reactions (ALTR) or osteolysis, often leading to premature implant failure. The tissue response can be best characterized by histopathological analysis, which accurately determines the presence of cell types, but is limited in the characterization of biochemical changes (e.g. protein conformation alteration). Fourier transform infrared micro-spectroscopy imaging (FTIRI) enables rapid analysis of the chemical structure of biological tissue with a high spatial resolution, and minimal additional sample preparation. The data provides the most information through multivariate method carried out by hierarchical clustering analysis (HCA). It is the goal of this study to demonstrate the beneficial use of this multivariate approach in providing pathologist with biochemical information from cellular and subcellular organization within joint capsule tissue retrieved from THR patients. Joint capsule tissue from 2 retrieved THRs was studied. Case 1: a metal-on-polyethylene THR, and Case 2: a dual modular metal-on-metal THR. Prior to FTIRI analysis, tissue samples were formalin-fixed paraffin-embedded and 5μm thick microtome sectioned samples were prepared and mounted on BaF. 2. discs and deparaffinized. FTIRI data were collected using high-definition transmission mode (pixel size: ∼1.1 μm. 2. ). Hyperspectral images were exported to CytoSpec V2.0.06 for processing and reconstruction into pseudo-color maps based on cluster assignments. Case 1 exhibited a strong presence of lymphocytes and
Introduction. Wear debris and metal ions originating from metal on metal hip replacements have been widely shown to recruit and activate
Introduction. Little is known about the relationship between head-neck corrosion and its effect on periprosthetic tissues and distant organs in the majority of patients hosting apparently well-functioning devices. We studied the degree and type of taper damage and the histopathologic response in periprosthetic tissue and distant organs. Methods. A total of 50 contemporary THRs (34 primary, 16 revision) retrieved postmortem from 40 patients after 0.4–26 years were studied. Forty-three femoral stems were CoCrMo and 7 were Ti6Al4V. In every case, a CoCrMo-alloy head articulated against a cementless polyethylene cup (19 XLPE and 31 UHMWPE). H&E and IHC sections of the joint pseudocapsules and liver were graded 1–4 for the intensity of various inflammatory cell infiltrates and tissue necrosis. The nature of the tissue response in the joint capsule, liver, spleen, kidneys and lymph nodes was assessed. Wear and corrosion products in the tissues were identified using SEM and EDS. Taper surfaces were graded for corrosion damage using modified Goldberg scoring and examined by SEM to determine the acting corrosion mode. Correlations between damage scores and the histologic variables were generated using the Spearman test. Results. No correlation was seen between taper damage scores and the
Aim. This study describes the histologic changes seen with a gentamicin-eluting synthetic bone graft substitute (BGS)(1) in managing bone defects after resection of chronic osteomyelitis (cOM). Method. 154 patients with mean follow-up of 21.8 months (12–56) underwent treatment of cOM with an antibiotic-loaded BGS for defect filling. Nine patients had subsequent surgery, not related to infection recurrence, allowing biopsy of the implanted material. These biopsies were harvested between 19 days and two years after implantation, allowing a description of the material's remodelling over time. Samples were fixed in formalin and stained with haematoxylin-eosin. Immunohistochemistry, using an indirect immunoperoxidase technique, identified the osteocyte markers Dentine Matrix Protein-1 (DMP-1) and Podoplanin, the
Introduction. Aseptic loosening is a major cause of revision of total joint arthroplasty (TJA). Although crosslinked Ultra-high molecular weight polyethylene (UHMWPE) have improved wear resistance, residual radicals remaining in the material have a possibility to increase bio-reactivity of particles [2]. In this study, we attempt to evaluate the effects of irradiation and residual radicals on bio-reactivity of the material with a new method called the inverse culture method [1]. Material and methods. UHMWPE particles (10µm diameter in average, Mitsui chemicals Co., LTD) along with irradiated particles (RAD, 300kGy electron irradiation) and particles annealed after the irradiation (RAD+ANN, 100°C 72 hours) are co-incubated with mouse
Undifferentiated pleomorphic sarcoma (UPS) is one of the most common and aggressive adult soft tissue sarcomas (STS). Once metastatic, UPS is rapidly fatal. Most STS, including UPS, are resistant to conventional immunotherapies as these tumours have low numbers of spontaneous tumour infiltrating lymphocytes (TILs) and are densely populated with immune suppressive
Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for
INTRODUCTION. Loosening is concerned to be the major cause of revision in the artificial prosthesis. Wear debris of UHMWPE dispersed into the implant-bone interface are phagocytosed by
Little is known about the relationship between head-neck corrosion and its effect on the periprosthetic tissues and distant organs of patients hosting well-functioning devices. The purpose of this study was to investigate in postmortem retrieved specimens the degree and type of taper damage, and the corresponding histologic responses in periprosthetic tissues and distant organs. Fifty postmortem THRs (34 primaries, 16 revisions) retrieved after 0.5 to 26 years were analyzed. Forty-three implants had a CoCrMo stem and seven had a Ti6Al4V stem. All heads were CoCrMo and articulated against polyethylene cups (19 XLPE, 31 UHMWPE). H&E sections of joint pseudocapsules, liver, spleen, kidneys and lymph nodes were graded 1–4 for the intensity of various inflammatory cell infiltrates and tissue characteristics. Corrosion damage of the taper surfaces was assessed using visual scoring and quantitated with an optical coordinate measuring machine. SEM analysis was used to determine the acting corrosion mode. Polyethylene wear was assessed optically. The majority of tapers had minimal to mild damage characterized by local plastic deformation of machining line peaks. Imprinting of the stem topography onto the head taper surface was observed in 18 cases. Column damage on the head taper surface occurred in three cases. All taper surfaces scored moderate or severe exhibited local damage features of fretting and/or pitting corrosion. Moderate or severe corrosion of the head and/or trunnion was present in nine hips. In one asymptomatic patient with bilateral hips, lymphocyte-dominated tissue reactions involving perivascular infiltrates of lymphocytes and plasmacytes were observed. In this patient, mild, focal lymphocytic infiltrates were also present in the liver and kidneys, and there was focal histiocytosis and necrosis of the para-aortic lymph nodes. These two implants, which had been in place for 58.6 and 60.1 months, had severe intergranular corrosion of the CoCrMo trunnion, and column damage and imprinting on the head taper. In the other 41 hips,