Analysis of modular taper fractures of the revision hip stem Prevision and comparison of the original and current taper design.

Aims: The risk of mechanical failure of modular revision hip stems is frequently mentioned in the literature, but little is currently known about the actual clinical failure rates of this type of prosthesis. The current retrospective long-term analysis examines the distal and modular failure patterns of the Prevision hip stem from 18 years of clinical use. A design improvement of the modular taper was introduced in 2008, and the data could also be used to compare the original and the current design of the modular connection. Methods: We performed an analysis of the Prevision modular hip stem using the manufacturer's vigilance database and investigated different mechanical failure patterns of the hip stem from January 2004 to December 2022. Results: Two mechanical failure patterns were identified: fractures in the area of the distal fluted profile (distal stem fracture) and failure of the modular taper (modular fracture). A failure rate of 0.07% was observed for distal stem fracture, and modular fracture rates of 1.74% for the original and 0.013% for the current taper design. Conclusion: A low risk of mechanical failure for both fracture types was observed compared to other known complications in revision hip arthroplasty. In addition, the data show that a design change did significantly reduce the risk of a modular fracture.

Mid-term results of a cementless hip stem in femoral revision: how much diaphyseal press-fit do we need?

INTRODUCTION: The aim of this retrospective study was to analyze the clinical and functional outcome of a modular tapered revision hip stem after mid-term follow-up with a special focus on the length of the distal bicortical fixation of the cementless hip stem. MATERIALS AND METHODS: Follow-up examination was carried out for all patients with implantation of the Prevision hip stem between 2014 and 2019 to collect demographic, functional, and radiographic data. RESULTS: 44 patients with stem in situ were examined, and 61 patients could be included in the Kaplan-Meier survival analysis. Oxford's hip score was 37.3 at the mean follow-up of 4.0 years. Two hip stem revisions were performed due to periprosthetic infection, which resulted in a hip stem survival rate of 96.7% (CI: 87.4-99.1%) at the final follow-up of 7.5 years. No aseptic hip stem revision was required. The length of bicortical distal fixation was in the interquartile range of 6.8 to 9.0 cm, which was associated with good bone healing and a low rate of subsidence (4.5%). Implant-associated complications were observed in 10 cases (21.7%). CONCLUSIONS: The modular revision hip stem provides promising results at medium-term follow-up, with satisfactory clinical and functional outcomes comparable to other modular revision hip stems. The presented length of bicortical distal fixation shows the practice of the study center and was associated with good implant survival, bone healing and radiological results. REGISTRATION: Clinicaltrials.gov registration: NCT04833634 registered on April 6, 2021.

A silicone fiber coating as approach for the reduction of fibroblast growth on implant electrodes.

In cochlear implant (CI) patients, an increase in electrode impedance due to fibrotic encapsulation is frequently observed. Several attempts have been proposed to reduce fibroblast growth at the electrode contacts, but none proved to be satisfactory so far. Here, a silicone fiber coating of the electrode contacts is presented that provides a complex micro-scale surface topography and increases hydrophobicity to inhibit fibroblast growth and adhesion. A silicone fiber electrospinning process was developed to create a thin and porous fiber mesh. Fiber coatings were applied on graphite specimen holders, glass cover slips and CI electrode contacts. For characterization of the coating's pore distribution, water contact angle and electrical impedance were analyzed. Cytotoxicity and in vitro fibroblast growth were evaluated to assess biological efficacy of the coatings. It could be shown that the silicone fiber mesh itself had only minor influence on electrode impedance. A uniform, hydrophobic fiber coating could be achieved that decreased fibroblast growth without showing toxic effects. Finally, CI electrode contacts were successfully coated in order to present this promising approach for a long-term improvement of CI electrodes. We are one of the first groups that could successfully adapt the electrospinning technique on the utilization of silicone. Silicone was chosen because of its high hydrophobicity, chemical stability and excellent biocompatibility and as it is one of the biomaterials already used in CIs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2574-2580, 2017.

Outer electrospun polycaprolactone shell induces massive foreign body reaction and impairs axonal regeneration through 3D multichannel chitosan nerve guides.

We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts.

Dipyridamole-related enhancement of gap junction coupling in the GM-7373 aortic endothelial cells correlates with an increase in the amount of connexin 43 mRNA and protein as well as gap junction plaques.

Previous data showed that dipyridamole enhanced gap junction coupling in vascular endothelial and smooth muscle cell lines by a cAMP-dependent mechanism. The present study investigates the level at which dipyridamole affects gap junction coupling. In the GM-7373 endothelial cell line, scrape loading/dye transfer experiments revealed a rapid increase in gap junction coupling induced during the first 6 h of dipyridamole treatment, followed by a slow increase induced by further incubation. Immunostaining analyses showed that the rapid enhancement of gap junction coupling correlated with an increased amount of Cx43 gap junction plaques and a reduced amount of Cx43 containing vesicles, while the amount of Cx43 mRNA or protein was not changed during this period, as found by semiquantitative RT-PCR and Western blot. Additionally, brefeldin A did not block this short-term-induced enhancement of gap junction coupling. Along with the dipyridamole-induced long-term enhancement of gap junction coupling, the amount of Cx43 mRNA and protein additionally to the amount of Cx43 gap junction plaques were increased. Furthermore, the anti-Cx43 antibody detected only two bands at 42 kDa and 44 kDa in control cells and cells treated with dipyridamole for 6 h, while long-term dipyridamole-treated cells showed a third band at 46 kDa. We propose that a dipyridamole-induced cAMP synthesis increased gap junction coupling in the GM-7373 endothelial cell line at different levels: the short-term effect is related to already oligomerised connexins beyond the Golgi apparatus and the long-term effect involves new expression and synthesis as well as posttranslational modification of Cx43.

Biphasic increase of gap junction coupling induced by dipyridamole in the rat aortic A-10 vascular smooth muscle cell line.

The rat aortic smooth muscle cell line A-10 was used to investigate the effect of dipyridamole on the gap junction coupling of smooth muscle cells. The scrape loading/dye transfer (SL/DT) technique revealed that dipyridamole concentrations between 5 µM and 100 µM significantly increased gap junction coupling. The adenosine receptor antagonist MRS 1754, as well as the PKA inhibitors Rp-cAMPS and H-89 were able to inhibit the dipyridamole-related increase in coupling, while forskolin and Br-cAMP also induced an enhancement of the gap junction coupling. Regarding the time-dependent behaviour of dipyridamole, a short-term effect characterised by an oscillatory reaction was observed for application times of less than 5 h, while applications times of at least 6 h resulted in a long-term effect, characterised by a constant increase of gap junction coupling to its maximum levels. This increase was not altered by prolonged presence of dipyridamole. In parallel, a short application of dipyridamole for at least 15 min was found to be sufficient to evoke the long-term effect measured 6 h after drug washout. We propose that in both the short-term and long-term effect, cAMP-related pathways are activated. The short-term phase could be related to an oscillatory cAMP effect, which might directly affect connexin trafficking, assembly and/or gap junction gating. The long-term effect is most likely related to the new expression and synthesis of connexins. With previous data from a bovine aortic endothelial cell line, the present results show that gap junction coupling of vascular cells is a target for dipyridamole.

Purine receptors and Ca(2+) signalling in the human blood-brain barrier endothelial cell line hCMEC/D3.

The expression and physiology of purine receptors of the human blood-brain barrier endothelial cells were characterised by application of molecular biological, gene-silencing and Ca(2+)-imaging techniques to hCMEC/D3 cells. Reverse transcription polymerase chain reaction showed the expression of the G-protein-coupled receptors P2Y(2)-, P2Y(6)-, P2Y(11)- as well as the ionotropic P2X(4)-, P2X(5)- and P2X(7)-receptors. Fura-2 ratiometry revealed that adenosine triphosphate (ATP) or uridine triphosphate (UTP) mediated a change in the intracellular Ca(2+) concentration ([Ca(2+)](i)) from 150 to 300 nM in single cells. The change in [Ca(2+)](i) corresponded to a fourfold to fivefold increase in the fluorescence intensity of Fluo-4, which was used for high-throughput experiments. Pharmacological dissection using different agonists [UTPγS, ATPγS, uridine diphosphate (UDP), adenosine diphosphate (ADP), BzATP, αß-meATP] and antagonist (MRS2578 or NF340) as well as inhibitors of intracellular mediators (U73122 and 2-APB) showed a PLC-IP(3) cascade-mediated Ca(2+) release, indicating that the nucleotide-induced Ca(2+) signal was mainly related to P2Y(2, 6 and 11) receptors. The gene silencing of the P2Y(2) receptor reduced the ATP- or UTP-induced Ca(2+) signal and suppressed the Ca(2+) signal mediated by P2Y(6) and P2Y(11) more specific agonists like UDP (P2Y(6)), BzATP (P2Y(11)) and ATPγS (P2Y(11)). This report identifies the P2Y(2) receptor subtype as the main purine receptor involved in Ca(2+) signalling of the hCMEC/D3 cells.

An advanced cone-and-plate reactor for the in vitro-application of shear stress on adherent cells.

Endothelial cells (ECs) are permanently exposed to the blood flow and the resulting shear stress, its magnitude varying with the EC site in the blood stream. Along with other mechanical stimuli like vessel wall stretching or hydrostatic blood pressure, this shear stress modulates the endothelial cell function, morphology and gene expression. Here, we describe our improved cone-and-plate reactor that applies up to 10 dyn/cm(2) uniform wall shear stress on a defined, ring-shaped region on a culture dish. At the same time, a hydrostatic pressure of up to 195 mmHg can be applied by increasing the atmospheric pressure in the incubator box. Gas composition can be controlled additionally, used for maintaining CO2-homeostasis or inducing hypoxic conditions. For better comparability, six cone-and-plate systems can be used at the same time at different rotational velocities. The effects on cell morphology, cytoskeleton and cell alignment can be monitored during application using a laser scanning microscope. Flow conditions have been studied and a sufficient area of uniform wall shear stress could be shown. To exceed 10 dyn/cm2, we suggest an increase in medium viscosity.

CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains.

The adhesion receptor CD96 (TACTILE) is a transmembrane glycoprotein possessing three extracellular immunoglobulin-like domains. Among peripheral blood cells, CD96 is expressed on T cells as well as NK cells and a subpopulation of B cells. A possible function of this receptor in NK cell-mediated killing activities was suggested recently. Moreover, CD96 was described as a tumor marker for T-cell acute lymphoblastic leukemia and acute myeloid leukemia. CD96 binds to CD155 (poliovirus receptor) and nectin-1, an adhesion receptor related to CD155. Here we report that human but not mouse CD96 is expressed in two splice variants possessing either an I-like (variant 1) or V-like (variant 2) second domain. With the notable exception of an AML tumor sample, variant 2 predominates in all the CD96-expressing cell types and tissues examined. Using chimeric human/murine CD96 receptors, we show that the interaction with its ligands is mediated via the outermost V-like domain. In contrast to mouse, however, the binding of human CD96 to CD155 is sensitive to the characteristics of the two downstream domains. This is illustrated by a significantly weaker CD96/CD155 interaction mediated by variant 1 when compared with variant 2. Moreover, recent evidence suggested that mutations in human CD96 correlate with the occurrence of a rare form of trigonocephaly. One such mutation causing a single amino acid exchange in the third domain of human CD96 decreased the capacity of both variants to bind to CD155 considerably, suggesting that a CD96-driven adhesion to CD155 may be crucial in developmental processes.