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Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 8 - 8
1 Oct 2016
Young P Greer A Tsimbouri P Meek R Gadegaard N Dalby M
Full Access

We have developed precision-engineered strontium eluting nanopatterned surfaces. Nanotopography has been shown to increase osteoblast differentiation, and strontium is an element similar to calcium, which has been proven to increase new bone formation and mineralization. This combination has great potential merit in fusion surgery and arthroplasty, as well as potential to reduce osteoporosis. However, osteoclast mediated osteolysis is responsible for the aseptic failure of implanted biomaterials, and there is a paucity of literature regarding osteoclast response to nanoscale surfaces. Furthermore, imbalance in osteoclast/osteoblast resorption is responsible for osteoporosis, a major healthcare burden. We aimed to assess the affect of strontium elution nanopatterned surfaces on osteoblast and osteoclast differentiation.

We developed a novel human osteoblast/osteoclast co-culture system without extraneous supplementation to closely represent the in vivo environment. We assessed the surfaces using electron microscopy (SEM), protein expression using immunofluorescence and histochemical staining and gene expression using polymerase chain reaction (PCR).

In complex co-culture significantly increased osteoblast differentiation and bone formation was noted on the strontium eluting, nanopatterned and nanopatterned strontium eluting surfaces, suggesting improved osteointegration. There was a reduction in macrophage attachment on these surfaces as well, suggesting specific anti-osteoclastogenic properties of this surface.

Our results show that osteoblast and osteoclast differentiation can be controlled through use of nanopatterned and strontium eluting surface features, with significant bone formation seen on these uniquely designed surfaces.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 24 - 24
1 Oct 2016
Tsimbouri* P Holloway N Fisher L Sjostrom T Nobbs A Meek R Su B Dalby M
Full Access

Nanotopographical cues on Ti surfaces have been shown to elicit different cell responses such as differentiation and selective growth. Bone remodelling is a continuous process requiring specific cues for optimal bone growth and implant fixation. In addition, the prevention of biofilm formation on surgical implants is a major challenge. We have identified nanopatterns on Ti surfaces that would be optimal for both bone remodelling and for reducing risk of bacterial infection. We used primary human osteoblast/osteoclast co-cultures and seeded them on flat Ti and three Ti nanosurfaces with increasing degrees of roughness, manufactured using anodisation under alkaline conditions (for 2, 2.5 and 3 hours). Cell growth and behaviour was assessed by scanning electron microscopy (SEM), immunofluorescence microscopy, histochemistry and quantitative RT-PCR methods. Bacterial growth on the nanowire surfaces was also assessed by confocal microscopy and SEM. From the three surfaces tested, the 2 h nanowire surface supported osteoblast and, to a lesser extent, osteoclast growth and differentiation. Bacterial viability was significantly reduced on the 2h surface. Hence the 2 h surface provided optimal bone remodelling conditions while reducing infection risk, making it a favourable candidate for future implant surfaces. This work was funded by EPSRC grant EP/K034898/1.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 52 - 52
1 Oct 2016
Silverwood R Berry C Ahmed F Meek R Dalby M
Full Access

Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Upregulation of specific microRNAs has been identified in-vivo in osteoporotic patients. It is hypothesized that modulation of specific mircoRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease.

We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential upregulation of osteoblastogenesis without cessation of osteoclast activity.

The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on miRNA targeting.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_3 | Pages 14 - 14
1 Apr 2015
Halai M Augustine A Holloway N MacDonald D Mohammed A Meek R Patil S
Full Access

Two major challenges in arthroplasty are obesity and antibiotic resistance. This study was performed to characterise the organisms responsible for deep infection following total hip arthroplasty and to determine if obesity affected the microbiology profile.

A retrospective analysis of the national surgical site infection register was made to obtain data regarding deep infection following 10948 primary total hip arthroplasty (THA) from 1998–2013, with a minimum of 2 year follow-up.

Of all the primary THAs performed, there were 108 deep infections (56 patients had a BMI >30 (obese) and 52 patients <30). There were no significant differences between cardio-respiratory disease, smoking and alcohol status, and diabetes between the 2 groups. Over the last 15 years, staphylococcus aureus continues to be the most frequently isolated organism. Infection with multiple organisms was found exclusively in obese patients. Furthermore, in obese patients, there was a linear increase with methicillin resistant staphylococcus aureus (MRSA) infections and streptococcus viridans.

On this basis, we recommend careful selection of antibiotic therapy in obese patients, rather than empirical therapy, which can be especially important if there is no growth in an infected THA. In addition, a preoperative discussion regarding dental prophylaxis against streptococcus viridans may be warranted.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_3 | Pages 16 - 16
1 Apr 2015
Marsh A Crighton E Yapp L Kelly M Jones B Meek R
Full Access

Successful treatment of periprosthetic joint infection involves surgical intervention and identification of infecting organisms to enable targeted antibiotic therapy. Current guidelines recommend intra-operative culture sampling to include at least 4 tissue samples and for each sample to be taken with a separate instrument.

We aimed to review current revision arthroplasty practice for Greater Glasgow, specifically comparing intra-operative sampling technique for infected revision cases with these guidelines.

We reviewed the clinical notes of all patients undergoing lower limb revision arthroplasty procedures in Greater Glasgow Hospitals (WIG, GRI, SGH) from July 2013 to August 2014. Demographics of all cases were collected. For revision procedures performed for infection we recorded details of intraoperative samples taken (number, type and sampling technique) and time for samples to reach the laboratory. Results of microbiology cultures were reviewed.

Two hundred and fifty five revision arthroplasty procedures (152 hips, 103 knees) were performed in the 12 month study period. Of these 57 (22%) were infected cases (28 hips, 29 knees). These cases were treated by 14 arthroplasty surgeons with a median number of 3 infected cases managed per surgeon (range 1–11). 58% of cases had the recommended number of tissue samples taken. The median number of microbiology samples collected was 4 (range 1–14). Most procedures (91%) had no documentation of whether separate instruments were used for sampling. Number of tissue samples taken (≥4, p=0.01), time to lab (<24 hours, p=0.03) were significantly associated with positive culture results.

In Greater Glasgow, a large number of surgeons manage infected arthroplasty cases with variability in intra-operative sampling techniques. Sample collection adheres to guideline recommendations in 58% cases. Adhering to guideline standards increases the likelihood of positive tissue cultures. Implementation of a standardised approach to intra-operative sampling for infected cases may improve patient management.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_3 | Pages 17 - 17
1 Apr 2015
Brydone A Morrison D Meek R Dalby M Gadegaard N
Full Access

Poly-ether-ether-ketone (PEEK) is a biomaterial commonly used for spinal implants and screws. It is often desirable for orthopaedic implants to osseointegrate, but as PEEK is biologically inert this will not occur. The aim of this project was to determine if injection mould nanopatterning can be used to create a make PEEK bioactive and stimulate osteogenesis in vitro.

PEEK substrates were fabricated by injection mould nanopatterning to produce near-square (NSQ) nanopatterned PEEK and planar (FLAT) PEEK samples. Atomic force microscopy (AFM) and scanning electron microscopy were used to characterize the surface topography. Human bone marrow stromal cells (hBMSCs) were isolated from patients undergoing primary hip replacement operations and seeded onto the PEEK substrates. After 6 weeks the cells were stained using alizarin red S (ARS) stain (to detect calcium) and the von Kossa technique (to detect phosphate) and analyzed using CellProfiler image analysis software to determine: surface coverage; cell number; and expression of either calcium (ARS stain) or phosphate (von Kossa technique).

ARS stain showed calcium expression (quantified relative to the number of cells) was increased on NSQ PEEK compared to FLAT PEEK (not statistically significant) and the surface coverage was similar. Von Kossa staining revealed more surface coverage on FLAT PEEK (69.1% cf. 31.9%), cell number was increased on FLAT PEEK (9803 ± 4066 cf. 4068 ± 1884) and phosphate expression relative to cell number was also increased (seven-fold) on NSQ PEEK (P < 0.05) compared to FLAT PEEK.

Although hBMSCs may adhere to NSQ PEEK in smaller numbers, the cells expressed a relatively larger amount of calcium and phosphate. This indicates that the cells adopted a more osteoblastic phenotype and that nanopatterning PEEK induces hBMSC differentiation and stimulates osteogenesis. Injection mould nanopatterning therefore has the potential to improve osseointegration of PEEK implants in vivo.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_7 | Pages 9 - 9
1 Apr 2014
Marsh A Nisar A El Refai M Meek R Patil S
Full Access

When performing total hip replacements in patients with hip dysplasia, acetabular augmentation may be required to prevent early component failure. Preoperative radiographic templating may help estimate acetabularcomponent coverage but has not previously been shown to predict the need for augmentation.

We developed a simple method to estimate the percentage of acetabular component coverage from pre-operative radiographs (True: False cup ratio). We aimed to evaluate whether this couldpredict the need foracetabular augmentation at primary total hip replacement for patients with dysplastic hips.

We reviewed all patients with hip dysplasia who underwent a primary total hip replacement from 2005–2012. Classification of hip dysplasia (Crowe), centre edge angle (CEA), Sharp and Tonnis angles were determined on pre-operative radiographs for each patient. Templating was performed on anteroposteriorand lateral view hip radiographs to determine the likely percentage of acetabular component coverage using the True: False cup ratio. Patients requiring acetabular augmentation at time of primary total hip arthroplasty were noted.

128 cases were reviewed, 31 (24%) required acetabularaugmentation. Comparison between augmented and non-augmented cases revealed no difference in the mean CEA (p = 0.19), Sharp angles (p = 0.76) or Tonnis angles (p = 0.32). A lower True Cup: False Cup ratio was observed in the augmented groupcompared to the non-augmented group(median = 0.68 vs 0.88, p < 0.01).

Preoperative templating can help predict which dysplastic hips are likely to require acetabular augmentation at primary total hip replacement.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_7 | Pages 7 - 7
1 Apr 2014
Silverwood R Fairhurst P Tsimbouri P Sjostrom T Young P Su B Meek R Dalby M
Full Access

Background

Aseptic loosening remains the primary reason for failure of orthopaedic implants. Therefore a prime focus of Orthopaedic research is to improve osteointegration and outcomes of joint replacements. The topography of a material surface has been shown to alter cell adhesion, proliferation and growth. The use of nanotopography to promote cell adhesion and bone formation is hoped to improve osteointegration and outcomes of implants. We have previously shown that 15nm high features are bioactive. The arrangement of nanofeatures has been shown to be of importance and block-copolymer separation allows nanopillars to be anodised into the titania layer, providing a compromise of control of order and height of nanopillars. Osteoblast/osteoclast stem cell co-cultures are believed to give the most accurate representation of the in vivo environment, allowing assessment of bone remodelling related to biomaterials.

Aims

To assess the use of nanotopography on titania substrates when cultured in a human bone marrow derived co-culture method.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 2 - 2
1 Aug 2013
Gupta S Maclean M Anderson J MacGregor S Meek R Grant M
Full Access

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.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 36 - 36
1 Aug 2013
Herd J Joseph J McGarvey M Tsimbouri P Bennett A Meek R Morrison A
Full Access

Allogenic blood is a finite resource, with associated risks. Previous studies have shown intra-operative cell salvage (ICS) can reduce allogenic transfusion rates in orthopaedic surgery. However, recent concerns regarding the efficacy and cost-effectiveness of ICS mean we must continually re-assess its usefulness in current practice. This study was carried out to review the use of ICS, to establish if its use has led to a reduction in patient exposure to post-op allogenic transfusion.

All orthopaedic patients who underwent ICS and re-infusion between 2008–2010 in the Southern General Hospital (SGH) were audited. The Haemoglobin (Hb) drop, volume of blood re-infused and post-op allogenic transfusion rates were recorded. The revision hip group was compared to a similar SGH cohort, who underwent surgery by the same surgeons between 2006–2008, and a pre-2005 control group. The Cell Saver (Haemonetics) machine was used.

The proportion of patients who received a post-op allogenic transfusion fell by 55% in the 2008–2010 ICS cohort compared with the control, and by 40% compared with the previous ICS study group. In both instances, this was accompanied by a statistically significant (p<0.001) reduction in mean number of units transfused per patient.

ICS has been shown to be effective in reducing rates and volume of post-op allogenic transfusion in patients undergoing revision hip surgery at the SGH. ICS has been used with increasing efficiency over time.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 37 - 37
1 Aug 2013
Leitch A Joseph J Murray H McMillan T Meek R
Full Access

Over 70,000 hip fractures occur annually in the UK. Both SIGN (111) and NICE (124) give guidance on optimal management of these patients. Both suggest cemented hemiarthroplasty should be used in those without contra-indications, as cemented implants are associated with less thigh pain, subsidence and a better functional outcome. Cardiorespiratory compromise secondary to bone cement implantation syndrome (BCIS) is however a concern in those with pre-existing cardiorespiratory disease (NYHA grade 3–4, pulmonary hypertension) or pathological fracture [3].

The aim of our study was to audit the practice of a University of Glasgow hospital with regard to cemented hemiarthroplasty.

We retrospectively reviewed data on all patients treated with hemiarthroplasty for hip fracture at the Southern General Hospital between 01/01/12-02/04/12. Patient demographics, pre-operative plan, procedure performed, ASA grade and pre-morbid mobility were recorded.

Results

Twenty-three hemiarthroplasties were performed. The median age was 82 (70–101). No patient aged over 90 underwent cemented hemiarthroplasty. Cemented implants (JRI, Furlong) were used in 26% (n=6) while 74% (n=17) underwent uncemented (Stryker, Austin-Moore) hemiarthroplasty. ASA grade was recorded in eight (35%). There were four ASA-2 patients (mild systemic disease not limiting activity) of which 75% underwent uncemented hemiarthroplasty. Pre-morbid mobility was recorded in eight (35%). All three independently mobile patients underwent uncemented hemiarthroplasty. Six (26%) had a documented pre-operative plan with regards to cement use.

This study highlights the disparity between current recommendations and our Centres’ practice. Most notable were: poor recording of pre-operative mobility, poor documentation of a pre-operative surgical plan, the low use of cemented fixation even in fit mobile patients and the lack of ASA grade recording (stratification of risk) by our anaesthetic colleagues.

We suggest a documented pre-operative discussion between the surgeon and anaesthetist to establish BCIS risk and decide on use of cemented arthroplasty taking into account age and mobility.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 4 - 4
1 Aug 2013
Marsh A Nisar A Patil S Meek R
Full Access

Repeat revision hip replacements can lead to severe bone loss necessitating salvage procedures such as proximal or total femoral replacement. We present medium term outcomes from our experience of the Limb Preservation System (LPS) in patients with failed revision hip arthroplasties.

All patients undergoing proximal femoral or total femoral replacement from 2003–2007 at our unit were reviewed. Data was collected preoperatively and at annual assessment post procedure for a minimum of 5 years. This included clinical review, functional outcome scores (WOMAC, Oxford Hip Score, Harris Hip Score) and radiographic evaluation.

A total of 17 patients underwent femoral replacement (13 proximal, 4 total) using the LPS during the study period. Within this cohort there were 13 males and 4 females with a mean age of 64 years (range 47–86). Median follow up was 7 years (range 5–9 years). Primary diagnoses were DDH (7), Primary OA (5), RA (2), proximal femoral fracture (2) and phocomelia (1). Five patients (29%) required further revision surgery for infection (2 patients) or recurrent dislocations (3 patients). No stems required revision due to aseptic loosening or stem failure at 5–9 years. Compared to preoperative assessment, there was significant improvement in median outcome scores at 5 years (WOMAC increased by 33 points, Oxford hip score by16 points and Harris hip score by 43 points). 82% of patients maintained functional independence at latest review.

The Limb Preservation System offers a salvage procedure for failed revision total hip arthroplasty with significant symptom and functional improvement in most patients at medium term follow up.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 50 - 50
1 Aug 2013
Robinson P Wilkinson A Meek R
Full Access

Metal on metal (MoM) bearings in hip surgery may result in increased blood levels of metal ions. The nature of the relationship between ion levels and failure is still not fully understood.

We compared three cohorts of resurfacing patients, grouped for brand and diameter of femoral component. We measured the blood level of Cobalt and Chromium ions at an average of 4 years postoperatively. The results were grouped as follows: Birmingham Hip Resurfacing ≥50 mm diameter, Durom resurfacing ≥50 mm diameter and Durom resurfacing <50 mm diameter.

120 patients were included in each group. There were significant differences in Cobalt levels between the groups. The median cobalt level for the BHR group was 8 nmol/L higher than the Durom ≥50 mm group (P<0.005). The Durom <50 mm group recorded cobalt levels 8.5 nmol/L higher than the Durom ≥50 mm group (P=0.0004). Revision rates were equal in the Large BHR's and Large Durom HRA (both 3.3%) however the small Durom HRA had a revision rate of 8.3%.

Elevated blood ion levels can indicate a failing MoM bearing. When similar ion levels were reported for BHR and small Durom the latter had significantly higher revision rates. The large BHR and large Durom HRA have similar revision rates yet the large Durom HRA had significantly lower metal ion levels. Only one of the patients having revision surgery (n=18) had metal ion levels above the MHRA threshold. This suggests ion levels do not absolutely predict the rate of HRA failure. Given similar revision rates with different ion levels between the large BHR and large Durom hips, mechanisms of failure leading to revision must be isolated from the release of metal ions. Therefore clinical and image based follow up are recommended in addition to ion level monitoring.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 2 - 2
1 Aug 2013
Brydone A Morrison D Meek R Dalby M Gadegaard N
Full Access

Polyetheretherketone (PEEK) is a thermoplastic polymer that is predominant in spinal surgery as the material of choice for spinal fusion cages, and is also used for bone anchors, cruciate ligament interference screws, and femoral stems. It has the distinct advantage of having similar mechanical properties to bone, but its clinical application as implant material is limited by a lack of bioactivity. This project aims to create an PEEK surface capable of osseointegration using a surface modification technique known as oxygen plasma treatment.

PEEK surfaces were injection molded, washed and then treated in a plasma chamber for up to 10 min. Surfaces were characterised using atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle measurements and X-ray photo-electron spectroscopy (XPS). Human bone marrow cells were cultured on the surfaces and assessed for calcium production (using alizarin red stain).

Water contact angle measurements show that after plasma treatment, the surfaces become very hydrophilic, before developing a meta-stable state at approx. 6 weeks. AFM and SEM showed destruction of the nano-pits at treatment durations longer than 2 mins. XPS detected a progressive increase in the atomic proportion of oxygen at the surface with increasing plasma treatment duration. There was significantly less alizarin uptake (and hence calcium production) on the untreated PEEK compared to the plasma treated PEEK surfaces (p < 0.05).

These results show that oxygen-plasma treatment can increase calcium production on PEEK surfaces and may improve long term osseointegration of PEEK implants.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_31 | Pages 54 - 54
1 Aug 2013
Gupta S Maclean M Anderson J MacGregor S Meek R Grant M
Full Access

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 arthroplasty 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 (123 mW/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 (greater than a 4-log reduction) was achieved for all of the clinical isolates from infected arthroplasty cases. The typical inactivation curve showed a slow initial reaction followed by a period of rapid inactivation. The doses of HINS-light exposure required ranged from 118–2214 J/cm2 respectively. Gram-positive bacteria were generally found to be more susceptible than Gram-negative.

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.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 20 - 20
1 Aug 2013
Elias-Jones C Reilly J Kerr S Meek R Patil S Kelly M Campton L McInnes I Millar N
Full Access

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.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_30 | Pages 54 - 54
1 Aug 2013
Davison M McMurray R Dalby M Meek R
Full Access

Osteogenesis is key to fracture healing and osteointegration of implanted material. Modification of surfaces on a nanoscale has been shown to affect cell interaction with the material and can lead to preferential osteogenesis. We hypothesised that osteogenesis could be induced in a heterogeneous population of osteoprogenitor cells by circular nanopits on a material surface. Furthermore, we intended to assess any correlation between nanopit depth and osteoinductive potential.

The desired topographies were embossed onto polycaprolactone (PCL) discs using pre-fabricated nickel shims. All pits had a diameter of 30μm and investigated pit depths were 80nm, 220nm and 333nm. Scanning electron microscopy confirmed successful embossing and planar controls were shown to be flat. A bone marrow aspirate was obtained from the femoral neck of a healthy adult undergoing a hip replacement. After establishing a culture, cells were seeded onto the PCL discs, suspended in basal media and incubated. Samples were fixed and stained after three and 28 days.

Cells were stained for the adhesion molecule vinculin after three days. Lowest concentrations of vinculin were seen in the planar control group. Osteoprogenitor cells on the shallowest pits, 80nm, had larger and brighter adhesion complexes. After 28 days, osteocalcin and osteopontin expression were used as markers of cell differentiation into an osteoblastic phenotype. 220nm deep pits consistently produced cells with the highest concentrations of osteopontin (p = 0.017) with a similar trend of osteocalcin expression. Cells on all topographies had higher expression levels than the planar controls.

We demonstrated stimulation of osteogenesis in a heterogeneous population of osteoprogenitor cells. This cell mix is similar to that present in fracture healing and after reaming for intramedullary devices or uncemented implants. All nanopit depths gave promising results with an optimum depth of 220nm after 28 days.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 77 - 77
1 Aug 2012
Lord J Langton D Nargol A Meek R Joyce T
Full Access

Metal-on-metal hip resurfacing prostheses are a relatively recent intervention for relieving the symptoms of common musculoskeletal diseases such as osteoarthritis. While some short term clinical studies have offered positive results, in a minority of cases there is a recognised issue of femoral fracture, which commonly occurs in the first few months following the operation. This problem has been explained by a surgeon's learning curve and notching of the femur but, to date, studies of explanted early fracture components have been limited.

Tribological analysis was carried out on fourteen retrieved femoral components of which twelve were revised after femoral fracture and two for avascular necrosis (AVN). Eight samples were Durom (Zimmer, Indiana, USA) devices and six were Articular Surface Replacements (ASR, DePuy, Leeds, United Kingdom). One AVN retrieval was a Durom, the other an ASR. The mean time to fracture was 3.4 months. The AVNs were retrieved after 16 months (Durom) and 38 months (ASR).

Volumetric wear rates were determined using a Mitutoyo Legex 322 co-ordinate measuring machine (scanning accuracy within 1 micron) and a bespoke computer program. The method was validated against gravimetric calculations for volumetric wear using a sample femoral head that was artificially worn in vitro. At 5mm3, 10mm3, and 15mm3 of material removal, the method was accurate to within 0.5mm3. Surface roughness data was collected using a Zygo NewView500 interferometer (resolution 1nm).

Mean wear rates of 17.74mm3/year were measured from the fracture components. Wear rates for the AVN retrievals were 0.43mm3/year and 3.45mm3/year. Mean roughness values of the fracture retrievals (PV = 0.754nm, RMS = 0.027nm) were similar to the AVNs (PV = 0.621nm, RMS = 0.030nm), though the AVNs had been in vivo for significantly longer.

Theoretical lubrication calculations were carried out which found that in both AVN retrievals and in seven of the twelve cases of femoral fracture the roughening was sufficient to change the lubrication regime from fluid film to mixed. Three of these surfaces were bordering on the boundary lubrication regime. The results show that even before the femoral fracture, wear rates and roughness values were high and the implants were performing poorly.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVIII | Pages 18 - 18
1 Jun 2012
Gupta S Gupta H Lomax A Carter R Mohammed A Meek R
Full Access

Cardiovascular disease is now the leading cause of morbidity and mortality worldwide. 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. The intraoperative measurements were compared with their baseline readings and their stress response, assessed using the Bruce protocol.

Many trends were noted in this pilot study. All of the surgeons had higher BP and HR readings on operating days compared to baseline. The physiological parameters normalised by one hour post-theatre list in all subjects. 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.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVIII | Pages 44 - 44
1 Jun 2012
Smith J Hussain S Horey L Patil S Meek R
Full Access

Hip resurfacing has generally been used in younger patients with early osteoarthritis of the hip. There has been considerable recent interest in this over the past few years. We conducted a prospective randomised trial comparing 2 hip resurfacing implants, Durom and ASR looking at radiological and clinical outcomes.

Forty-nine patients (78% male) with hip osteoarthritis which met the criteria for hip resurfacing were randomised to receive either a Durom or ASR resurfacing implant. These patients have so far been followed up for a minimum of one year. The groups were comparable in age (p=0.124) and gender (p=0.675). The average age in the ASR group was 54.04 years and in the Durom group it was 51.25.

Radiological views were scrutinised immediately post op and at final follow up so far to look at cup inclination, stem-shaft angle, and acetabular osseointegration.

Clinical outcomes were compared using the Oxford hip scores, WOMAC scores and SF12 scores.

At minimum follow up of 1 year the mean post operative Oxford hip score was not significantly different between the Durom (45.32, SD 3.93) and ASR (43.44, SD 8.44). The mean post operative WOMAC score was also not significantly different between the Durom (52.56, SD 6.06) and ASR (49.63, SD 2.23). There was no difference between the groups with regards to signs of osseointegration from radiological assessment (p=0.368). There were 3 periprosthetic femoral neck fractures (5.7%) and one revision for pain.

We conclude from this trial that there is no difference in the clinical or radiological findings between the Durom and ASR implants.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVIII | Pages 36 - 36
1 Jun 2012
Jamieson L Shaw L Horey L Wilkinson A Meek R Crawford J
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Prophylactic antibiotics administered prior to joint arthroplasty have become standard practice. Due to concern over the risk that 2nd generation cephalosporins posed to the elderly, as regards clostridium difficile associated infections the antimicrobial management team in our unit changed the protocol for prophylactic antibiotics. As of 1st September 2009, flucloxacillin and gentamicin were preferred over cefuroxime as the first choice of prophylactic antibiotic. However, it was noted that postoperatively patients were experiencing a decrease in renal function.

One hundred patients who underwent a total hip replacement following the policy change were randomly selected from the departmental joint arthroplasty database. This group was age and sex matched to 100 patients undergoing their surgery prior to the change. Data was collected on renal function, length of stay, antibiotic and age. Any change in renal function was categorised using the RIFLE criteria.

Exclusion secondary to variations from protocol or treatment for femoral neck fractures resulted in a total number of 156 patients with 78 in each arm. The average age for both groups was 64 years. Non-parametric analysis of preoperative and postoperative serum creatinine concentrations and Glomerular Filtration Rate (GFR) demonstrated a significant difference between the two groups, showing that GFR decreased (p=0.041) and serum creatinine concentration increased (p=0.037) in the cohort receiving gentamicin. Classing the impaired renal function as: risk, injury or failure (RIFLE criteria) demonstrated a statistically significant difference for any criterion positive (p=0.016) but no significant difference for the specific RIFLE groups (p=0.068).

Acknowledging the small numbers and potential confounders for renal impairment, this study was able to show a difference in renal function for patients receiving gentamicin over cefuroxime as prophylaxis for joint arthroplasty.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVIII | Pages 37 - 37
1 Jun 2012
Wilkinson A Meek R Dalby M
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It is well established that cell behaviour is responsive to the surrounding environment. Chemistry, material stiffness and topography allow control of cell adhesion, proliferation, growth and differentiation. Biomimicry is playing a role in the next generation of biomaterials, surface engineering on orthopaedic implants may promote improved skeletal integration.

Human osteoblasts were cultured on engineered micro-topographical features with nanoscale depths, similar in scale to an osteoclast resorption pit. Three different micro-topographies were used (in addition to planar controls.) created on a hot moulded polymer. The cells were cultured in basal media on surfaces with 20, 30 and 40 micrometer circular pits, each with a depth of 400 nanometers. The cells were fixed at time points 3 days, 21 days and 28 days to allow assessment of cytoskeletal development, production of protein markers of bone production (osteopontin) and mineral deposition respectively.

At each time point greater indicators of cell activity and bone production were evident on the 30 and 40 micrometer structures as compared with the 20 micrometer structures and the planar controls. These positive results include increased focal adhesions, stronger expression of intracellular and extracellular osteopontin and more mature nodules of calcium formation.

This in vitro study demonstrates that micro and nanotopographies influence cell activity. Osteoblast response can be induced on the surface of a future generation of orthopaedic implants, lasting long after the effects chemical application have expired. Further research is required to assess the potential application to implant grade materials.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVIII | Pages 31 - 31
1 Jun 2012
Hussain S Cairns D Mann C Horey L Patil S Meek R
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The objective was to compare vastus lateralis muscle splitting verses muscle sparing surgical approach to proximal femur for fixation of intertrochanteric fracture.

Of the 16 patients in this prospective randomised double blind study 8 were randomised to vastus lateralis muscle splitting and rest to muscle sparing group. Main outcome measurement was assessment of status of vastus lateralis muscle at 2 and 6 weeks using nerve conduction study. Preoperative demographics were identical for both the groups.

There was no statistically significant difference between the groups with regards to velocity, latency, and amplitude. The postoperative haemoglobin drop, heamatocrit, position of the dynamic hip screw and mobility status were identical.

Both clinical and neurophysiological outcome suggest that damage done to vastus lateralis either by splitting or elevating appears to be identical.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 31 - 31
1 May 2012
Findlay C Jameson S Marshall S Walker B Walker C Meek R Nicol A
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Background

Following an anterior cruciate ligament (ACL) injury, the affected knee is known to experience bone loss and is at significant risk of becoming osteoporotic. Surgical reconstruction is performed to attempt to restore the function of the knee and theoretically restore this bone density loss. Cross-sectional analysis of the proximal tibia using peripheral quantitative computed tomography (pQCT) enables localised analysis of bone mineral density (BMD) changes. The aim of this study was to establish the pattern of bone density changes in the tibia pre- and post- ACL reconstruction using pQCT image analysis.

Methods

Eight patients who underwent ACL reconstruction were included. A cross sectional analysis of the proximal tibia was performed using a pQCT scanner pre-operatively and one to two years post-operatively on both the injured and contralateral (control) knee. The proximal two and three percent slices [S2 and S3] along the tibia were acquired. These were exported to Matlab(tm) and automated segmentation was performed to remove the tibia from its surrounding structures. Cross correlation was applied to co-register pairs of images and patterns of change in BMD were mapped using a t-test (p<0.05). Connected components of pixels with significant change in BMD were created and used to assess the impact of ACL injury & reconstruction on the proximal tibial BMD.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XI | Pages 14 - 14
1 Apr 2012
Gupta S Augustine A Horey L Meek R Hullin M Mohammed A
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Anterior knee pain following primary total knee replacement (TKR) is a common problem with average reported rates in the literature of approximately 10%. Symptoms are frequently attributed to the patellofemoral joint, and the treatment of the patella during total knee replacement is controversial.

There is no article in the literature that the authors know of that has specifically evaluated the effect of patella rim cautery on TKR outcome. This is a denervation technique that has historically been employed, with no evidence base. A prospective comparative cohort study was performed to compare the outcome scores of patients who underwent circumferential patella rim cautery, with those who did not.

Patients who had undergone a primary TKR were identified from the unit's arthroplasty database. Two cohorts, who were age and gender matched, were established. None of the patients had their patella resurfaced, but all had a patellaplasty. The Low Contact Stress TKR (Depuy International) was used in all cases.

The effect of circumferential patella rim cautery on the Oxford Knee Score (OKS) and the more anterior knee pain specific Patellar Score (PS) a minimum of 2 years post surgery was evaluated. Previous reports have suggested that a change of 5 points in the OKS represents a clinical difference. A sample size calculation based on an effect size of 5 points with 80% power and a p-value of 0.05 would require a minimum of 76 patients in each group.

There were 94 patients who had undergone patellaplasty only, and 98 patients who had supplementary circumferential patella rim cautery during their primary TKR. The mean OKS were 34.61 and 33.29 respectively (p=0.41), while the PS scores were 21.03 and 20.87 (p=0.87).

No statistically significant differences were noted between the groups for either outcome score. Patella rim cauterisation is unnecessary in primary TKR.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XI | Pages 1 - 1
1 Apr 2012
Augustine A Horey L Murray H Craig D Meek R Patil S
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The diagnosis and treatment of hip disease in young adults has rapidly evolved over the past ten years. Despite the advancements of improved diagnostic skills and refinement of surgical techniques, the psychosocial impact hip disease has on the young adult has not yet been elucidated.

This observational study aimed to characterise the functional and psychosocial characteristics of a group of patients from our young hip clinic. 49 patients responded to a postal questionnaire which included the Oswestry Disability Index (ODI) and Hospital Anxiety and Depression Scale (HADS). Median age was 20 years (range 16-38) with a gender ratio of 2:1 (female: male). The most common diagnoses were Perthes' disease and developmental hip dysplasia. More than half of our patients had moderate to severe pain based on the Visual Analogue Scale (VAS) and at least a moderate disability based on the ODI. Thirty-two percent of patients were classified as having borderline to abnormal levels of depression and 49% of patients were classified as having borderline to abnormal levels of anxiety based on the HADS. Comparison of the ODI with the VAS and HADS anxiety and depression subscales showed a significant positive correlation (p<0.05). Multiple regression showed the ODI to be a significant predictor of the HADS anxiety and depression scores (regression coefficient 0.13, 95% confidence interval 0.06 to 0.21, p<0.05).

This study highlights the previously unrecognised psychosocial effects of hip disease in the young adult. A questionnaire which includes HADS may be of particular value in screening for depression and anxiety in young people with physical illness. This study also highlights that collaboration with psychologists and other health care providers may be required to achieve a multidisciplinary approach in managing these patients.