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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 48 - 48
1 Dec 2021
Alkhrayef MN Hotchen AJ McCaskie AW Birch MA
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Abstract

Objectives

Mesenchymal stromal/stem cells (MSCs) are increasingly recognized as regulators of immune cells during disease or tissue repair. During these situations, the extracellular matrix (ECM) is very dynamic and therefore, our studies aim to understand how ECM influences the activity of MSCs.

Methods

Human MSCs cultured on tissue culture plastic (TCP) and encapsulated within collagen type I, fibrin, or mixed Collagen-Fibrin were exposed to low dose TNFα and IFNɣ. Transcription profiles were examined using bulk RNA sequencing (RNAseq) after 24h of treatment. ELISA, Western blot, qPCR and immunofluorescence were employed to validate RNAseq results and to investigate the significance of transcriptional changes. Flow cytometry evaluated monocyte/macrophage phenotype.


Bone & Joint Research
Vol. 10, Issue 9 | Pages 611 - 618
27 Sep 2021
Ali E Birch M Hopper N Rushton N McCaskie AW Brooks RA

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

Methods

Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization.


Bone & Joint Open
Vol. 2, Issue 4 | Pages 261 - 270
1 Apr 2021
Hotchen AJ Khan SA Khan MA Seah M Charface ZH Khan Z Khan W Kang N Melton JTK McCaskie AW McDonnell SM

Aims

To investigate factors that contribute to patient decisions regarding attendance for arthroplasty during the COVID-19 pandemic.

Methods

A postal questionnaire was distributed to patients on the waiting list for hip or knee arthroplasty in a single tertiary centre within the UK. Patient factors that may have influenced the decision to attend for arthroplasty, global quality of life (QoL) (EuroQol five-dimension three-level (EQ-5D-3L)), and joint-specific QoL (Oxford Hip or Knee Score) were assessed. Patients were asked at which ‘COVID-alert’ level they would be willing to attend an NHS and a “COVID-light” hospital for arthroplasty. Independent predictors were assessed using multivariate logistic regression.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 373 - 378
1 May 2018
Johnson-Lynn SE McCaskie AW Coll AP Robinson AHN

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration.

Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy.

It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis.

Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14).

Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process.

An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking.

Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373–378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 1 - 2
1 Jan 2015
Haddad FS McCaskie AW

Trauma and Orthopaedic care has been through a rapid evolution over the past few decades. This Editorial discusses some of the advances.

Cite this article: Bone Joint J 2015;97-B:1–2.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_13 | Pages 48 - 48
1 Mar 2013
Kalaskar DM Mohanti A McCaskie AW Birch MA
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Controlled differentiation of Human mesenchymal stem cells (hMSCs) is required for timely induction of bone growth in implantable biomaterials. Differentiation of hMSCs towards a particular lineage depends upon their microenvironment, which is a complex mixture of various physical, chemical and biological parameters. The role of Bone morphogenic protein (BMP2) in early induction of bone formation is well established. Clinical experience and in vitro study has shown that presentation of this protein in small quantities by surface immobilisation significantly induces osteogenic differentiation compared to large quantities provided in solution. This project focuses on developing and understanding responsive micro/nano porous interfaces which deliver BMP2 in a dose dependent fashion to control osteogenic diffentiation of hMSCs. We hypothesise that use of porous membranes primed with LbL deposition of biomacromolecules such as COL and HA will help in induction of cell attachment and growth whilst controlled and localised delivery of BMP2 released from the layers of these porous constructs will induce sustained differentiation of hMSCs. By controlling pore size of membranes, rate of release of BMP2 can be controlled. We use fluorescently labelled Dextran (Flu-DEX) as model protein to study control release mechanism, which is of similar size to BMP2. Polycarbonate (PC) track etched membranes with various pore sizes were used for LbL assembly of COL/HA/Flu-DEX along with hydrolytically degradable polymer Poly-Beta amino ester (Poly2). Six bilayers were constructed into porous membranes with (COL-Flu-DEX)6 and (Poly2-Flu-DEX)6. Use of hydrolytically degradable polymer significantly enhances release of Flu-DEX compared to control (COL-Flu-DEX)6 assembly. Compared to flat (non porous) surface, release from porous samples maintained a relatively slow and steady release. We are currently investigating release of BMP2 using this approach and their influence on the differentiation of hMSCs in vitro


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 5 - 8
1 Jan 2007
Deehan DJ Bell K McCaskie AW

Interest in football continues to increase, with ever younger age groups participating at a competitive level. Football academies have sprung up under the umbrella of professional clubs in an attempt to nurture and develop such talent in a safe manner. However, increased participation predisposes the immature skeleton to injury. Over a five-year period we have prospectively collected data concerning all injuries presenting to the medical team at Newcastle United football academy. We identified 685 injuries in our cohort of 210 players with a mean age of 13.5 years (9 to 18). The majority of injuries (542;79%) were to the lower limb. A total of 20 surgical procedures were performed. Contact injuries accounted for 31% (210) of all injuries and non-contact for 69% (475).The peaks of injury occurred in early September and March. The 15- and 16-year-old age group appeared most at risk, independent of hours of participation. Strategies to minimise injury may be applicable in both the academy setting and the wider general community.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1596 - 1602
1 Dec 2006
Muller SD Deehan DJ Holland JP Outterside SE Kirk LMG Gregg PJ McCaskie AW

The role of modular tibial implants in total knee replacement is not fully defined. We performed a prospective randomised controlled clinical trial using radiostereophotogrammetric analysis to compare the performance of an all-polyethylene tibia with a metal-backed cruciate-retaining condylar design, PFC-∑ total knee replacement for up to 24 months. There were 51 patients who were randomised into two treatment groups. There were 10 subsequent withdrawals, leaving 21 all-polyethylene and 20 metal-backed tibial implants. No patient was lost to follow-up. There were no significant demographic differences between the groups. At two years one metal-backed implant showed migration > 1 mm, but no polyethylene implant reached this level. There was a significant increase in the SF-12 and Oxford knee scores after operation in both groups.

In an uncomplicated primary total knee replacement the all-polyethylene PFC-∑ tibial prosthesis showed no statistical difference in migration from that of the metal-backed counterpart. There was no difference in the clinical results as assessed by the SF-12, the Oxford knee score, alignment or range of movement at 24 months, although these assessment measures were not statistically powered in this study.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1117 - 1117
1 Aug 2006
HOLLANS JP LOUGHEAD JM McCASKIE AW


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 237 - 237
1 May 2006
Sprowson AP McCaskie AW Birch MA
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Background A biomaterial serves to support, organize and directly influence the behaviour of growing cells. Chitosan has the capability to be a very useful biomaterial in the speciality of orthopaedics, due to its excellent biocompatibility, and physical properties that allow topographical modification. Chitosan films have potential to be used to coat implant surfaces, regulating bone cells at the implant interface. Enhanced integration may therefore help towards solving problems such as aseptic loosening.

Method 85% deacylated chitosan (Sigma) was dissolved in 2% acetic overnight. The viscous chitosan was then sterilized by autoclaving for 10 minutes. PDMS patterned stamps produced from a silicon mould were added to the viscous chitosan and as the chitosan film forms the topographic impression is left on the surface. The gel was then dried for 36 hours in a sterile system. The pH is neutralized with NaOH1M for 24 hours. The gel was washed in sterile hanks balanced salt solution until the pH was 7.4. Osteoblasts were then grown on these surfaces in a cell culture system and analysed by light microscopy and image analysis.

Results We have successfully designed a protocol for the production of sterile topographically modified chitosan, with surface features that can be produced in the range of 1–100um. We have shown that cells on un-modified chitosan differentiate and form bone at a much slower rate than on chitosan with a modified surface. Findings supported by in-situ alkaline phosphatase levels. Control can be exerted on cell shape and inter-cellular interactions based upon shape and surface area between shapes; with a smaller surface area making adhesion more difficult.

Conclusion. Our data shows that osteoblasts can be controlled by altering chitosans surface topography. Being able to influence biology by changing biomaterial surface features will enhance interaction at the bone implant interface, allowing greater implant integration.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 31 - 34
1 Jan 2006
Loughead JM Starks I Chesney D Matthews JNS McCaskie AW Holland JP

Resurfacing arthroplasty of the hip is being performed more frequently in the United Kingdom. The majority of these patients are younger than 55 years of age, and in this group the key benefits include conservation of femoral bone stock and the potential reduction in the rate of dislocation afforded by the larger resurfacing head. Early aseptic loosening is well recognised in patients younger than 55 years of age, and proponents of resurfacing believe that the improved wear characteristics of the metal-on-metal bearing may improve the long-term survival of this implant. There has been some concern, however, that resurfacing may not be conservative of acetabular bone.

We compared a series of 33 consecutive patients who had a hybrid total hip arthroplasty with an uncemented acetabular component and a cemented femoral implant, with 35 patients undergoing a Birmingham hip resurfacing arthroplasty. We compared the diameter of the implanted acetabulum in both groups and, because they were not directly comparable, we corrected for patient size by measuring the diameter of the contralateral femoral head. The data were analysed using unpaired t-tests and analysis of covariance.

There was a significantly larger acetabulum in the Birmingham arthroplasty group (mean diameter 56.6 mm vs 52.0 mm; p < 0.001). However, this group had a significantly larger femoral head diameter on the contralateral side (p = 0.03). Analysis of covariance revealed a significant difference between the mean size of the acetabular component implanted in the two operations. The greatest difference in the size of acetabulum was in those patients with a larger diameter of the femoral head. This study shows that more bone is removed from the acetabulum in hip resurfacing than during hybrid total hip arthroplasty, a difference which is most marked in larger patients.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_II | Pages 145 - 145
1 Apr 2005
Loughead JM Phaltankar P Mitchell S McCaskie AW Lingard EA Deehan DJ
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Statement of purpose: To evaluate survivorship and knee function in patients who have undergone Kinematic Condylar Total Knee Replacement at a minimum of 15 years.

Methods: We evaluated all patients undergoing primary cemented TKR with the Kinematic Condylar implant (Howmedica), between January 1981 and December 1988. All operations were performed by a single surgeon through a medial parapatellar approach, with sparing of the PCL, all cemented and no patellae resurfaced.

Operation notes were analysed to confirm the type of procedure, underlying diagnosis, and thickness of tibial insert. Information was derived from patient records and postal questionnaire to all surviving patients, which included: WOMAC, SF-36, satisfaction scale and history of revision surgery.

Results: We have identified a total of 804 consecutive cases, 185 of these were bilateral giving a total of 619 patients. Mean age at implantation was 66 (range 17 to 83), with female:male ratio of 3:1. The underlying diagnosis was Osteoarthritis in 49%, and Rheumatoid Arthritis in 51% of patients.

As at September 2003 there were 153 patients (25%) still alive, using revision as an endpoint survivorship was 59.3% at a mean time since implantation of 17 years 8 months. Pain and function portions of the WOMAC questionnaire revealed mean scores of 37 and 47 out of 100.

Conclusion: This cohort has been shown to have 92% implant survivorship at ten years. We have shown that the survivorship deteriorates significantly between 10 and 17 years. Functional and pain scores after 17 years for patients with surviving implants were poor.

Survival was significantly better in females, no effect from pre-operative diagnosis was seen. 73% of these patients had 6mm tibial inserts, we postulate that the deterioration in survival is related to accelerated poly-ethylene wear beyond 10 years.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 163 - 166
1 Feb 2005
Loughead JM Chesney D Holland JP McCaskie AW

Hip resurfacing is being performed more frequently in the United Kingdom. The possible benefits include more accurate restoration of leg length, femoral offset and femoral anteversion than occurs after total hip arthroplasty (THA).

We compared anteroposterior radiographs from 26 patients who had undergone hybrid THA (uncemented cup/cemented stem), with 28 who had undergone Birmingham Hip Resurfacing arthroplasty (BHR). We measured the femoral offset, femoral length, acetabular offset and acetabular height with reference to the normal contralateral hip. The data were analysed by paired t-tests.

There was a significant reduction in femoral offset (p = 0.0004) and increase in length (p = 0.001) in the BHR group. In the THA group, there was a significant reduction in acetabular offset (p = 0.0003), but femoral offset and overall hip length were restored accurately. We conclude that hip resurfacing does not restore hip mechanics as accurately as THA.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 8 | Pages 1214 - 1219
1 Nov 2004
Jafri AA Green SM Partington PF McCaskie AW Muller SD

Fatigue fractures which originate at stress-concentrating voids located at the implant-cement interface are a potential cause of septic loosening of cemented femoral components. Heating of the component to 44°C is known to reduce the porosity of the cement-prosthesis interface.

The temperature of the cement-bone interface was recorded intra-operatively as 32.3°C. A simulated femoral model was devised to study the effect of heating of the component on the implant-cement interface.

Heating of the implant and vacuum mixing have a synergistic effect on the porosity of the implant-cement interface, and heating also reverses the gradients of microhardness in the mantle.

Heating of the implant also reduces porosity at the interface depending on the temperature. A minimum difference in temperature between the implant and the bone of 3°C was required to produce this effect. The optimal difference was 7°C, representing a balance between maximal reduction of porosity and an increased risk of thermal injury. Using contemporary cementing techniques, heating the implant to 40°C is recommended to produce an optimum effect.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 6 | Pages 838 - 842
1 Aug 2001
Chambers IR Fender D McCaskie AW Reeves BC Gregg PJ

The radiological features of the cement mantle around total hip replacements (THRs) have been used to assess aseptic loosening. In this case-control study we investigated the risk of failure of THR as predictable by a range of such features using data from patients recruited to the Trent Regional Arthroplasty Study (TRAS).

An independent radiological assessment was undertaken on Charnley THRs with aseptic loosening within five years of surgery and on a control group from the TRAS database. Chi-squared tests were used to test the probability of obtaining the observed data by chance, and odds ratios were calculated to estimate the strength of association for different features.

Several features were associated with a clinically important increase (> twofold) in the risk of loosening, which was statistically significant for four features (p < 0.01). Inadequate cementation (Barrack C and D grades) was the most significant feature, with an estimated odds ratio of 9.5 (95% confidence interval 3.2 to 28.4, p < 0.0001) for failure.


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 1 | Pages 167 - 170
1 Jan 1999
Reading AD McCaskie AW Gregg PJ

Radiological assessment of the cement mantle is used routinely to determine the outcome of total hip replacement. We performed a simulated replacement arthroplasty on cadaver femora and took standard postoperative radiographs. The femora were then sectioned into 7 mm slices starting at the calcar, and high-resolution faxitron radiographs were taken of these sections.

Analysis of the faxitron images showed that defects in the cement mantle were observed up to 100 times more frequently than on the standard films. We therefore encourage the search for a better technique in assessing the cement mantle.


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 6 | Pages 971 - 975
1 Nov 1998
McCaskie AW Deehan DJ Green TP Lock KR Thompson JR Harper WM Gregg PJ

Early implants for total knee replacement were fixed to bone with cement. No firm scientific reason has been given for the introduction of cementless knee replacement and the long-term survivorship of such implants has not shown any advantage over cemented forms. In a randomised, prospective study we have compared cemented and uncemented total knee replacement and report the results of 139 prostheses at five years. Outcome was assessed both clinically by independent examination using the Nottingham knee score and radiologically using the Knee Society scoring system.

Independent statistical analysis of the data showed no significant difference between cemented and cementless fixation for pain, mobility or movement. There was no difference in the radiological alignment at five years, but there was a notable disparity in the radiolucent line score. With cemented fixation there was a significantly greater number of radiolucent lines on anteroposterior radiographs of the tibia and lateral radiographs of the femur.

At five years, our clinical results would not support the use of the more expensive cementless fixation whereas the radiological results are of unknown significance. Longer follow-up will determine any changes in the results and conclusions.


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 3 | Pages 379 - 384
1 May 1997
McCaskie AW Barnes MR Lin E Harper WM Gregg PJ

The newer techniques of cementing aim to improve interlock between cement and bone around a femoral stem by combining high pressure and reduced viscosity. This may produce increased embolisation of fat and marrow leading to hypotension, impaired pulmonary gas exchange and death. For this reason the use of high pressures has been questioned.

We compared finger-packing with the use of a cement gun by measuring intramedullary pressures during the cementing of 31 total hip replacements and measuring physiological changes in 19 patients. We also measured pressure in more detail in a laboratory model.

In the clinical series the higher pressures were produced by using a gun, but this caused less physiological disturbance than finger-packing. The laboratory studies showed more consistent results with the gun technique, but for both methods of cementing the highest pressures were generated during the insertion of the stem of the prosthesis.


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 2 | Pages 191 - 194
1 Mar 1996
McCaskie AW Brown AR Thompson JR Gregg PJ

Three radiological methods are commonly used to assess the outcome of total hip replacement (THR). They aim to record the appearance of lucent areas and migration of the prosthesis in a reproducible manner. Two of them were designed to monitor the implant through time and one to grade the quality of cementing. We have measured the level of inter- and intraobserver agreement in all three systems.

We randomised 30 patients to receive either finger packing or retrograde gun cementing during Charnley hip replacements. The postoperative departmental radiographs were evaluated in a blinded study by two orthopaedic trainees, two consultants and two experts in THR. The trainees and consultants repeated the exercise at least two weeks later. We used the unweighted kappa statistic to establish the levels of agreement.

In general, intraobserver agreement was moderate but interobserver agreement was poor, with levels similar to or less than those expected by chance. Our results indicate that such systems cannot provide reliable data from centres in different parts of the world, with various levels of surgeon evaluating radiographs at differing time intervals. We discuss the problem and suggest some methods of improvement.