The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells. HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.Aims
Methods
To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDAims
Methods
Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology.Aims
Methods
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Aims
Methods
This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys. Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment.Aims
Methods
Early evidence has emerged suggesting that ceramic-on-ceramic
articulations induce a different tissue reaction to ceramic-on-polyethylene
and metal-on-metal bearings. Therefore, the aim of this study was
to investigate the tissue reaction and cellular response to ceramic
total hip arthroplasty (THA) materials We investigated tissue collected at revision surgery from nine
ceramic-on-ceramic articulations. we compared our findings with
tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene
THAs, and four primary osteoarthritis synovial membranes. The latter
were analyzed to assess the amount of tissue fibrosis that might
have been present at the time of implantation to enable evaluation,
in relation to implantation time, of any subsequent response in
the tissues.Aims
Patients and Methods
The acetabular labrum is a soft-tissue structure
which lines the acetabular rim of the hip joint. Its role in hip
joint biomechanics and joint health has been of particular interest
over the past decade. In normal hip joint biomechanics, the labrum
is crucial in retaining a layer of pressurised intra-articular fluid
for joint lubrication and load support/distribution. Its seal around
the femoral head is further regarded as a contributing to hip stability through
its suction effect. The labrum itself is also important in increasing
contact area thereby reducing contact stress. Given the labrum’s
role in normal hip joint biomechanics, surgical techniques for managing
labral damage are continuously evolving as our understanding of
its anatomy and function continue to progress. The current paper
aims to review the anatomy and biomechanical function of the labrum
and how they are affected by differing surgical techniques. Take home message: The acetabular labrum plays a critical role
in hip function and maintaining and restoring its function during
surgical intervention remain an essential goal. Cite this article:
The aim of this study was to assess the effect
of frictional torque and bending moment on fretting corrosion at
the taper interface of a modular femoral component and to investigate
whether different combinations of material also had an effect. The
combinations we examined were 1) cobalt–chromium (CoCr) heads on
CoCr stems 2) CoCr heads on titanium alloy (Ti) stems and 3) ceramic
heads on CoCr stems. In test 1 increasing torque was imposed by offsetting the stem
in the anteroposterior plane in increments of 0 mm, 4 mm, 6 mm and
8 mm when the torque generated was equivalent to 0 Nm, 9 Nm, 14
Nm and 18 Nm. In test 2 we investigated the effect of increasing the bending
moment by offsetting the application of axial load from the midline
in the mediolateral plane. Increments of offset equivalent to head
+ 0 mm, head + 7 mm and head + 14 mm were used. Significantly higher currents and amplitudes were seen with increasing
torque for all combinations of material. However, Ti stems showed
the highest corrosion currents. Increased bending moments associated
with using larger offset heads produced more corrosion: Ti stems
generally performed worse than CoCr stems. Using ceramic heads did
not prevent corrosion, but reduced it significantly in all loading
configurations. Cite this article:
Abnormal wear of cobalt-containing metal-on-metal
joints is associated with inflammatory pseudotumours. Cobalt ions
activate human toll-like receptor 4 (TLR4), which normally responds
to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4
by LPS increases the expression of chemokines IL-8 and CXCL10, which
recruit leukocytes and activated T-cells, respectively. This study
was designed to determine whether cobalt induces a similar inflammatory
response to LPS by promoting the expression of IL-8 and CXCL10.
A human monocytic cell line, derived from acute monocytic leukaemia,
was treated with cobalt ions and expression of IL-8 and CXCL10 measured at
mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold
increase in IL-8 mRNA, and an eightfold increase in production of
the mature chemokine (both p <
0.001); expression of the CXCL10
gene and protein was also significantly increased by cobalt (both
p <
0.001). Experiments were also performed in the presence of
CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated
increase in IL-8 and CXCL10 expression. These findings suggest that cobalt ions induce inflammation similar
to that observed during sepsis by the simultaneous activation of
two TLR4-mediated signalling pathways. These pathways result in
increased production of IL-8 and CXCL10, and may be implicated in
pseudotumour formation following metal-on-metal replacement. Cite this article:
This preliminary study evaluates a combination
of bone morphogenetic protein (BMP)-7 and non-vascularised autologous
fibular grafting (AFG) for the treatment of osteonecrosis of the
femoral head. BMP-7/AFG combination was applied in seven pre-collapse femoral
heads (five Steinberg stage II, two stage III) in six patients.
Pre- and post-operative evaluation included clinical (Harris hip
score (HHS), visual analogue scale (VAS) for pain) and radiological
assessment (radiographs, quantitative CT) at a mean follow-up of
4 years (2 to 5.5). A marked improvement of function (mean HHS increase of 49.2)
and decrease of pain level (mean VAS decrease of 5) as well as retention
of the sphericity of the femoral head was noted in five hips at
the latest follow-up, while signs of consolidation were apparent
from the third post-operative month. One patient (two hips) required
bilateral total hip replacement at one year post-operatively. In
the series as a whole, quantitative-CT evaluation revealed similar densities
between affected and normal bone. Heterotopic ossification was observed
in four hips, without compromise of the clinical outcome. In this limited series AFG/BMP-7 combination proved a safe and
effective method for the treatment of femoral head osteonecrosis,
leading to early consolidation of the AFG and preventing collapse
in five of seven hips, while the operative time and post-operative
rehabilitation period were much shorter compared with free vascularised fibular
grafts. Cite this article:
In the majority of patients with slipped upper
femoral epiphysis only one hip is involved at primary diagnosis. However,
the contralateral hip often becomes involved over time. There are
no reliable factors predicting a contralateral slip. Whether or
not the contralateral hip should undergo prophylactic fixation is
a matter of controversy. We present a number of essential points
that have to be considered both when choosing to fix the contralateral
hip prophylactically as well as when refraining from surgery and
instead following the patients with repeat radiographs.
We developed a method of applying vibration to the impaction bone grafting process and assessed its effect on the mechanical properties of the impacted graft. Washed morsellised
Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly popular. Improved wear characteristics mean that these articulations are being inserted into younger patients in the form of THR and resurfacing procedures. This has led to concerns regarding potential carcinogenicity because of the increased exposure to metal ions that the procedure brings. We have studied the serum cobalt and chromium concentrations in patients who had primary, well-fixed Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and chromium were elevated by five and three times, respectively compared with those in our reference groups. Metal-on-metal articulations appear to be the source of metal ions throughout the life of the prosthesis. In three patients who had undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene replacement the levels of metal ions were within the normal range. The elevations of cobalt and chromium ions seen in our study were comparable with those in patients with modern metal-on-metal THRs.
Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p <
0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p >
0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p <
0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p >
0.05) The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer.