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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 144 - 144
11 Apr 2023
Lineham B Altaie A Harwood P McGonagle D Pandit H Jones E
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Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions.

PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared.

9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies.

This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 33 - 33
1 Mar 2021
Koria L Farndon M Lavalette D Jones E Mengoni M Brockett C
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Abstract

Objectives

Over 1% of the global population suffers with ankle osteoarthritis (OA), yet there is limited knowledge on the changes to subchondral bone with OA. In other joints, it has been shown that bone becomes osteosclerotic, with fewer, thicker trabeculae that become hypomineralised, causing an increased apparent bone volume fraction (BV/TV). Microstructural alterations reduce overall joint strength, which may impact the success of late-stage surgical interventions, such as total ankle arthroplasty (TAA). Previous ankle studies have evaluated changes to cartilage, bone plate and bone morphology with OA, hence this study aimed to characterise changes to trabecular architecture.

Methods

Three ankle joints were isolated from non-diseased cadaveric feet (three males: 43, 50 and 57 years, MEEC 18-027). Cylindrical subchondral bone specimens (N=6, 6.5 mm Ø) were extracted from the tibial plafond. Osteoarthritic bone samples (N=6, distal tibia) were sourced from local patients (three males: 65, 58 and 68 years, NREC 07/Q1205/27) undergoing TAA surgery. Specimens were imaged using µCT at a 16 µm isotropic resolution (µCT-100 ScanCo Medical). Virtual cores of bone (6.5 mm Ø) were extracted from the image data of the osteoarthritic specimens and trimmed to a height of 4 mm. BoneJ was used to evaluate key morphological indices: BV/TV; anisotropy (DA); trabecular thickness (Tb.Th); trabecular density (Conn.D) and ellipsoid factor (EF) which characterises rod/plate geometry. Differences between the two groups of specimens were evaluated using a t-test with Bonferroni correction.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 7 - 7
1 Jan 2019
Owston H Moisley K Tronci G Giannoudis P Russell S Jones E
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The current ‘gold’ standard surgical intervention for critical size bone defect repair involves autologous bone grafting, that risks inadequate graft containment and soft tissue invasion. Here, a new regenerative strategy was explored, that uses a barrier membrane to contain bone graft. The membrane is designed to prevent soft tissue ingrowth, whilst supporting periosteal regrowth, an important component to bone regeneration. This study shows the development of a collagen-based barrier membrane supportive of periosteal-derived mesenchymal stem cell (P-MSC) growth.

P-MSC-homing barrier membranes were successfully obtained with nonaligned fibres, via free-surface electrospinning using type I collagen and poly(E-caprolactone) in 1,1,1,3,3,3-Hexafluoro-2-propanol. Introduction of collagen in the electrospinning mixture was correlated with decreased mean fibre diameter (d: 319 nm) and pore size (p: 0.2–0.6 μm), with respect to collagen-free membrane controls (d: 372 nm; p: 1–2 μm). Consequently, as the average MSC diameter is 20 μm, this provides convincing evidence of the creation of a MSC containment membrane.

SEM-EDX confirmed Nitrogen and therefore collagen fibre localisation. Quantification of collagen content, using Picro Sirius Red dye, showed a 50% reduction after 24 hours (PBS, 37 °C), followed by a drop to 25% at week 3. The collagen-based membrane has a significantly higher elastic modulus compared to collagen-free control membranes. P-MSCs attached and proliferated when grown onto collagen-based membranes, imaged using confocal microscopy over 3 weeks. A modified transwell cell migration assay was developed, using MINUSHEET® tissue carriers to assess barrier functionality. In line with the matrix architecture, the collagen-based membrane proved to prevent cell migration (via confocal microscopy) in comparison to the migration facilitating positive control.

The aforementioned results obtained at molecular, cellular and macroscopic scales, highlight the applicability of this barrier membrane in a new ‘hybrid graft’ regenerative approach for the surgical treatment of critical size bone defects.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_11 | Pages 12 - 12
1 Oct 2015
Legerlotz K Jones E Riley G
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Introduction

The exact mechanisms leading to tendinopathies and tendon ruptures remain poorly understood while their occurrence is clearly associated with exercise. Overloading is thought to be a major factor contributing to the development of tendon pathologies. However, as animal studies have shown, heavy loading alone won't cause tendinopathies. It has been speculated, that malfunctioning adaptation or healing processes might be involved, triggering tendon tissue degeneration. By analysing the expression of the entirety of degrading enzymes (degradome) in pathological and non-pathological, strained and non-strained tendon tissue, the aim of this study was to identify common or opposite patterns in gene regulation. This approach may generate new targets for future studies.

Materials and Methods

RNA was extracted from different tendon tissues: normal (n=7), tendinopathic (n=4) and ruptured (n=4) Achilles tendon; normal (n=4) and tendinopathic (n=4) posterior tibialis tendon; normal hamstrings tendon with or without subjection to static strain (n=4). The RNA was reverse transcribed, then pooled per group The expression of 538 protease genes was analysed using Taqman low-density array quantitative RT-PCR. To be considered relevant, changes had to be at least 4fold and measurable at a level below 36 Cts.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_11 | Pages 26 - 26
1 Oct 2015
Udeze C Jones E Riley G Morrissey D Screen H
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Introduction

Tendinopathies are debilitating and painful conditions. They are believed to result from repetitive overuse, which can create micro-damage that accumulates over time, and initiates a catabolic cell response. The aetiology of tendinopathy remains poorly understood, therefore the ideal treatment remains unclear. However, current data support the use of eccentric exercise as an effective treatment. In a previous study, we have shown that eccentric loading generates perturbations in the tendon at 10Hz, which is not present during other less effective loading regimes. Consequently, we hypothesis that 10Hz loading initiates an increased anabolic response in tenocytes, that can promote tendon repair.

Materials and Methods

Human tenocytes from healthy hamstring tendons and tendinopathic Achilles tendons were derived by collagenase digest and outgrowth respectively. Tenocytes were seeded into 3D collagen gels. The gels were fixed in custom-made chambers and placed in an incubator for 24hrs whilst gene expression stabilised. After 24hrs, cyclic uniaxial strain at 1% ± 1% was applied to the cells, at either 1Hz (n=4) or 10Hz (n=4) using a Bose loading system. After 15 minutes of cyclic strain, the samples were maintained in chambers under 1% static strain for 24 hrs after which gene expression was characterised using RT-PCR.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 161 - 161
1 Jul 2014
Jones E Legerlotz K Riley G
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Summary Statement

We have shown that integrin mRNA expression is regulated by the application of mechanical load. This indicates that mechanical loading may modify cell sensitivity to perceive further load through increased interaction with the ECM.

Introduction

Tendinopathies are a range of diseases characterised by pain and insidious degeneration. Although poorly understood, onset is often associated with physical activity. We have previously investigated the regulation by mechanical strain of metalloproteinase gene expression in human tenocyte in a 3D collagen matrix. Integrins are important in cellular interaction with the ECM and are reported to mediate mechanotransduction in various non-tendon tissues. We have reported that TGFbeta activation is a key player in the regulation of metalloproteinases in response to mechanical load, which may be mediated by integrins. This project aims to investigate the effect of cyclic loading and TGFbeta stimulation on integrin expression by human tenocytes, in collagen and fibrin matrices.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 8 - 8
1 Aug 2012
Tan H Jones E Kozera L Henshaw K McGonagle D Giannoudis P
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Background and objectives

Fracture healing represents a physiological process regulated by a variety of signalling molecules, growth factors and osteogenic progenitor cells. Bone healing following trauma is associated with increased serum concentrations of several pro-inflammatory and angiogenic growth factors1. Platelet-derived growth factor (PDGF) has been shown to stimulate mesenchymal stem cell (MSC) proliferation in vitro. However, the in vivo relationship between the levels of PDGF and the numbers of MSCs in humans has not yet been explored. The aim of this study was to investigate PDGF release in the peripheral circulation following trauma and to correlate it with the numbers of MSCs in iliac crest bone marrow (BM) aspirate and in peripheral blood.

Methods

Trauma patients with lower extremity fractures (n=12, age 18-63 years) were recruited prospectively. Peripheral blood was obtained on admission, and at 1, 3, 5 and 7 days following admission. The serum was collected and PDGF was measured using the enzyme-linked immuno-sorbent assay (ELISA) technique. Iliac crest (BM) aspirate (20ml) and peripheral blood (PB) (20ml) was obtained on days 0-9 following admission. MSCs were enumerated using standard colony-forming unit fibroblasts (CFU-F) assay.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 35 - 35
1 May 2012
Cox G Giannoudis P Boxall S Buckley C Jones E McGonagle D
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Introduction

Iliac crest bone marrow aspirate (ICBMA) is frequently cited as the ‘gold-standard’ source of MSCs. MSCs have been shown to reside within the intramedullary (IM) cavities of long-bones [Nelea, 2005] however a comparative assessment with ICBMA has not yet been performed and the phenotype of the latter compartment MSCs remains undefined in their native environment.

Methods

Aspiration of the IM cavities of 6 patients' femurs with matched ICBMA was performed. The long-bone-fatty-bone-marrow (LBFBM) was filtered (70μm) to separate liquid and solid fractions and the solid fraction was briefly (60min, 37oC) digested with collagenase. MSC enumeration was performed using the colony-forming-unit-fibroblast (CFU-F) assay and quantification of cells with the CD45low CD271+ phenotype by flow-cytometry. [Jones 2002, Buhring 2007] MSCs were cultured and standard expansion media and passage 2 cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVIII | Pages 5 - 5
1 May 2012
Cox G McGonagle D Boxall S Buckley C Jones E Giannoudis P
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Introduction

Therapeutic exploitation of MSCs in orthopaedics has been tempered by their scarcity within ‘gold-standard’ iliac crest bone marrow aspirate (ICBMA) and the resulting need to expand cells in vitro. This is time-consuming, expensive and results in cells with a reduced differentiation capacity. [Banfi 2000] The RIA is a device that provides continuous irrigation and suction during reaming of long bones. Aspirated contents pass via a filter, trapping bony-fragments, before moving into a ‘waste’ bag, from which MSCs have been previously isolated. [Porter 2009] We hypothesised that ‘waste’ RIA bag contains more MSCs than a standard aspirated volume of ICBMA (30 ml). We further hypothesised than a fatty solid phase within this ‘waste bag’ contains many MSCs trapped within the adipocyte-rich stromal network and hence requiring an enzymatic digestion for their efficient release [Jones 2006].

Methods

The discarded filtrate ‘waste’ bag that contained saline from marrow cavity irrigation procedure from RIA reaming (7 patients) was filtered (70μm) and the solid fraction digested for 60min (37oC) with collagenase. MSC enumeration was performed using the colony-forming-unit-fibroblast (CFU-F). Following culture in standard expansion media, passage 2 cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages and their phenotype was assessed using flow cytometry. ICBMA from the same patients was used as controls.