National guidelines encourage the use of total hip arthroplasty (THA) to treat intracapsular neck of femur fractures. There have been no population based studies appraising the surgical outcomes for this indication across an entire population. This study aims to calculate the complication rates for THA when performed for a fractured neck of femur and compare them to THA performed for primary osteoarthritis in the same population. The Scottish Arthroplasty Project identified all THAs performed in Scotland for neck of femur fracture and osteoarthritis between 1st of January 2009 and 31st December 2014. Dislocation, periprosthetic infection and revision rates at 1 year were calculated. The rate of dislocation, periprosthetic infection and revision at 1 year were all significantly increased among the fracture neck of femur cohort. In total 44046 THAs were performed, 38316 for OA and 2715 for a neck of femur fracture. 2.1% of patients (n=57) who underwent a THA for a neck of femur fracture suffered a dislocation in the 1st year postoperatively, compared to 0.9% (n=337) when the THA was performed for osteoarthritis. Relative Risk of dislocation: 2.4 (95% C.I. 1.8077–3.1252, p value <0.0001). Relative Risk of infection: 1.5 (95% C.I. 1.0496–2.0200, p value 0.0245) Relative Risk of revision: 1.5 (95% C.I. 1.0308–2.1268, p value 0.0336). This is the first time a dislocation rate for THA performed for a neck of femur fracture has been calculated for an entire population. As the number of THAs for neck of femur fracture increases this dislocation rate will have clinical implications.
The burden of osteoporosis (OP), and its accompanied low energy fractures, is ever increasing. Targeted therapies are under development to stem the tide of the disease, with microRNAs identified as biomarkers and potential targets. Assessing the functional capacity of bone marrow mesenchymal stromal cells (BMSC) from patients with low energy neck of femur fractures (NOF) will identify the expected outcomes to be achieved from new, targeted osteogenic therapies. Two patient groups were assessed; low energy NOF and osteoarthritic. Bone marrow aspirates were taken at time of arthroplasty surgery. The adherent fraction was cultured and assessed by flow cytometry, microRNA expression and differentiation functionality. Both patient groups demonstrated characteristic extracellular markers of BMSCs. 3 key markers were significantly reduced in their expression in the NOF group (CD 90, 13, 166 P=0.0286). Reduced differentiation capacity was observed in the NOF group when cultured in osteogenic and adipogenic culture medium. 105 microRNAs were seen to be significantly dysregulated, with microRNAs known to be crucial to osteogenesis and disease process such as osteoporosis abnormally expressed. This data demonstrates the impaired functional capacity of BMSCs and their abnormal microRNA expression in patients who suffer a low energy NOF. Future targeted therapies for OP must address this to maximise their restorative effect on diseased bone. The important role microRNAs can play as biomarkers and target sites has been further reinforced.
In biomaterial engineering the surface of an implant can influence cell differentiation, adhesion and affinity towards the implant. Increased bone marrow derived mesenchymal stromal cell (BMSC) differentiation towards bone forming osteoblasts, on contact with an implant, can improve osteointegration. The process of micropatterning has been shown to improve osteointegration in polymers, but there are few reports surrounding ceramics. The purpose of this study was to establish a co-culture of BMSCs with osteoclast progenitor cells and to observe the response to micropatterned zirconia toughened alumina (ZTA) ceramics with 30 µm diameter pits. The aim was to establish if the pits were specifically bioactive towards osteogenesis or were generally bioactive and would also stimulate osteoclastogenesis that could potentially lead to osteolysis. We demonstrate specific bioactivity of micropits towards osteogenesis with more nodule formation and less osteoclastogenesis. This may have a role when designing ceramic orthopaedic implants.
Nanoscale topography increases the bioactivity of a material and stimulates specific responses (third generation biomaterial properties) at the molecular level upon first generation (bioinert) or second generation (bioresorbable or bioactive) biomaterials. We developed a technique (based upon the effects of nanoscale topography) that facilitated the Two topographies (nanopits and nanoislands) were embossed into the bioresorbable polymer Polycaprolactone (PCL). Three dimensional cell culture was performed using double-sided embossing of substrates, seeding of both sides, and vertical positioning of substrates. The effect of Hydroxyapatite, and chemical stimulation were also examined. Human bone marrow was harvested from hip arthroplasty patients, the mesenchymal stem cells culture expanded and used for cellular analysis of substrate bioactivity. The cell line specificity and osteogenic behaviour was demonstrated through immunohistochemistry, confirmed by real-time PCR and quantitative PCR. Mineralisation was demonstrated using alizarin red staining. Results showed that the osteoinduction was optimally conferred by the presence of nanotopography, and also by the incorporation of hydroxyapatite (HA) into the PCL. The nanopit topography and HA were both superior to the use of BMP2 in the production of mineralised bone tissue. The protocol from shim production to bone marrow harvesting and vertical cell culture on nanoembossed HaPCL has been shown to be reproducible and potentially applicable to economical larger scale production.
Infection rates following arthroplasty surgery are between 1–4%, with higher rates in revision surgery. The associated costs of treating infected arthroplasty cases are considerable, with significantly worse functional outcomes reported. New methods of infection prevention are required. HINS-light is a novel blue light inactivation technology which kills bacteria through a photodynamic process. The aim of this study was to investigate the efficacy of HINS-light for the inactivation of bacteria isolated from infected arthoplasty cases. Specimens from hip and knee arthroplasty infections are routinely collected to identify causative organisms. This study tested a range of these isolates for sensitivity to HINS-light. During testing, bacterial suspensions were exposed to increasing doses of HINS-light of (123mW/cm2 irradiance). Non-light exposed control samples were also set-up. Bacterial samples were then plated onto agar plates and incubated at 37°C for 24 hours before enumeration. Complete inactivation was achieved for all Gram positive and negative microorganisms More than a 4-log reduction in Staphylococcus epidermidis and Staphylococcus aureus populations were achieved after exposure to HINS-light for doses of 48 and 55 J/cm2, respectively. Current investigations using Escherichia coli and Klebsiella pneumoniae show that gram-negative organisms are also susceptible, though higher doses are required. This study has demonstrated that HINS-light successfully inactivated all clinical isolates from infected arthroplasty cases. As HINS-light utilises visible-light wavelengths it can be safely used in the presence of patients and staff. This unique feature could lead to possible applications such as use as an infection prevention tool during surgery and post-operative dressing changes.
Femoroacetabular impingement (FAI) is a significant cause of osteoarthritis in young active individuals but the pathophysiology remains unclear. Increasing mechanistic studies point toward an inflammatory component in OA. This study aimed to characterise inflammatory cell subtypes in FAI by exploring the phenotype and quantification of inflammatory cells in FAI versus OA samples. Ten samples of labrum were obtained from patients with FAI (confirmed pathology) during open osteochondroplasty or hip arthroscopy. Control samples of labrum were collected from five patients with osteoarthritis undergoing total hip arthroplasty. Labral biopsies were evaluated immunohistochemically by quantifying the presence of macrophages (CD68 and CD202), T cells (CD3), mast cells (mast cell tryptase) and vascular endothelium (CD34). Labral biopsies obtained from patients with FAI exhibited significantly greater macrophage, mast cell and vascular endothelium expression compared to control samples. The most significant difference was noted in macrophage expression (p<0.01). Further sub typing of macrophages in FAI using CD202 tissue marker revealed and M2 phenotype suggesting that these cells are involved in a regenerate versus a degenerate process. There was a modest but significant correlation between mast cells and CD34 expression (r=0.4, p<0.05) in FAI samples. We provide evidence for an inflammatory cell infiltrate in femoroacetabular impingement. In particular, we demonstrate significant infiltration of mast cells and macrophages suggesting a role for innate immune pathways in the events that mediate hip impingement. Further mechanistic studies to evaluate the net contribution and hence therapeutic utility of these cellular lineages and their downstream processes may reveal novel therapeutic approaches to the management of early hip impingement.
Raised blood pressures (BP) are associated with increased cardiovascular risks such as myocardial infarction, stroke and arteriosclerosis. During surgery the haemodynamic effects of stress are closely monitored and stabilised by the anaesthetist. Although there have been many studies assessing the effects of intraoperative stress on the patient, little is known about the impact on the surgeon. A prospective cohort study was carried out using an ambulatory blood pressure monitor to measure the BP and heart rates (HR) of three consultants and their respective trainees during hallux valgus, hip and knee arthroplasty surgery. Our principle aim was to assess the physiological effects of performing routine operations on the surgeon. We noted if there were any differences in the stress response of the lead surgeon, in comparison to when the same individual was assisting. In addition, we recorded the trainee's BP and HR when they were operating independently. All of the surgeons had higher BP and HR readings on operating days compared to baseline. When the trainer was leading the operation, their BP gradually increased until implant placement, while their trainees remained stable. On the other hand, when the trainee was operating and the trainer assisting, the trainer's BP peaked at the beginning of the procedure, and slowly declined as it progressed. The trainee's BP remained elevated throughout. The highest peaks for trainees were noted during independent operating. We conclude that all surgery is stressful, and that trainees are more likely to be killing themselves than their trainers.
