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Bone & Joint Research
Vol. 10, Issue 10 | Pages 659 - 667
1 Oct 2021
Osagie-Clouard L Meeson R Sanghani-Kerai A Bostrom M Briggs T Blunn G

Aims

A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing.

Methods

A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 650 - 658
1 Oct 2021
Sanghani-Kerai A Black C Cheng SO Collins L Schneider N Blunn G Watson F Fitzpatrick N

Aims

This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.

Methods

With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 677 - 689
1 Oct 2021
Tamaddon M Blunn G Xu W Alemán Domínguez ME Monzón M Donaldson J Skinner J Arnett TR Wang L Liu C

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Methods

The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 848 - 856
1 Dec 2020
Ramalhete R Brown R Blunn G Skinner J Coathup M Graney I Sanghani-Kerai A

Aims

Periprosthetic joint infection (PJI) is a debilitating condition with a substantial socioeconomic burden. A novel autologous blood glue (ABG) has been developed, which can be prepared during surgery and sprayed onto prostheses at the time of implantation. The ABG can potentially provide an antimicrobial coating which will be effective in preventing PJI, not only by providing a physical barrier but also by eluting a well-known antibiotic. Hence, this study aimed to assess the antimicrobial effectiveness of ABG when impregnated with gentamicin and stem cells.

Methods

Gentamicin elution from the ABG matrix was analyzed and quantified in a time-dependent manner. The combined efficiency of gentamicin and ABG as an anti-biofilm coating was investigated on titanium disks.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 402 - 411
1 Aug 2020
Sanghani-Kerai A Coathup M Brown R Lodge G Osagie-Clouard L Graney I Skinner J Gikas P Blunn G

Aims

For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel.

Methods

The autologous blood glue (ABG) that constituted 1.25, 2.5, and 5 times concentration PRP were made with and without equal volumes of BM nucleated cells. Proliferation, morphology, and viability of the cells in the glue was measured at days 7 and 14 and compared to cells seeded in fibrin glue.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 333 - 340
1 Jul 2020
Mumith A Coathup M Edwards TC Gikas P Aston W Blunn G

Aims

Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses.

Methods

A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 293 - 301
1 Jun 2020
Hexter AT Hing KA Haddad FS Blunn G

Aims

To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements.

Methods

A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization).


Bone & Joint Research
Vol. 8, Issue 8 | Pages 397 - 404
1 Aug 2019
Osagie-Clouard L Sanghani-Kerai A Coathup M Meeson R Briggs T Blunn G

Objectives

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1).

Methods

Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 12 - 12
1 Jan 2019
Sanghani-Kerai A Achilleos A Lanchashire H Coathup M Blunn G
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During remodelling, osteoclasts produce discrete bone cavities filled with bone and this is associated with the dimensions of the cavity. The aim of this study is to investigate the effect of pores of similar size to those produced by osteoclasts on the morphology, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. The hypothesis is that a porous surface similar in morphology to a bone surface prepared by osteoclasts will increase cell proliferation and osteogenic differentiation of MSCs.

Sheep BMSCs were seeded onto plain titanium surfaces and 100µm, 250µm and 500µm discrete pores surfaces. Cell metabolic activity was investigated using Presto Blue on days 3, 7 and 10. Bone mineralisation was quantified by Alizarin red staining at days 3, 7 and 14. Cell morphology was observed by scanning electron microscopy (SEM). Data was statistically analysed using one-way analysis of variance and a Bonferroni correction method.

Cells on porous discs had a three dimensional phenotype and aligned on the circumference of each pore. Metabolic activity was significantly higher by day 10 on plain discs compared to all porous discs. Bone mineralization was significantly higher on 100µm pores by day 3 (0.545mM±0.66; p=0.047) than plain discs and significantly higher on both 100µm and 250µm pores by day 7(p=0.000 and p=0.005) than plain discs. Substantial mineralised bone matrix was found on 100µm discs without being treated with osteogenic supplements, compared to other control disc types (p=0.043, p=0.003, p=0.000).

The different topographies altered cell behaviour and migration.100µm pores demonstrated earlier and enhanced bone mineralisation even in the absence of osteogenic supplements. This pore size is aligned to the size of individual resorption bays that osteoclasts produce on bone surfaces and is considerably lower than the pore sizes used to enhance osteo-integration of implant surfaces.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 11 - 11
1 Jan 2019
Giusto E Pendegrass C Liu C Blunn G
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Intraosseous Transcutaneous Amputation Prosthesis (ITAP) is a new generation of limb replacements that can provide to amputees, an alternative solution to the main problems caused by the most common used external prosthesis such as pressure sores, infections and unnatural gait. ITAP is designed as one pylon osteointegrated into the bone and protruding through the skin, allowing both the mechanical forces to be directly transferred to the skeleton and the external skin being free from frictions and infections. The skin attachment to the implant is fundamental for the success of the ITAP, as it prevents the implant to move and consequently fail.

In this study we wanted to test if cell viability and attachment was improved using TiO2 nanotubes.

Human keratinocytes and human dermal fibroblasts were seeded for three days on TiO2 nanotubes with different sizes (18–30nm, 40–60nm and 60–110nm), compared with controls (smooth titanium) and tested for viability and attachment. A Mann-Whitney U test was used to compare groups where p values < 0.05 were considered significant. The results showed that the viability and cell attachment for keratinocytes were significantly higher after three days on controls comparing with all nanotubes (p=0.02), while attachment was higher on bigger nanotubes and controls. Cell viability for fibroblasts was significantly higher on nanotubes between 40 and 110nm comparing with smaller size and controls (p=0.03), while investigation of cell attachment is ongoing.

From these early results, we can say that TiO2 nanotubes can improve the soft tissue attachment on ITAP. Further in-vitro and ex-vivo experiments on cell attachment will be carried out.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 4 - 4
1 Nov 2018
Meeson R Sanghani-kerai A Coathup M Blunn G
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A significant number of fractures develop non-union. Stem cell therapy may be beneficial in their treatment, however this requires acquisition, culture and delivery of stem cells. Stem cell homing and migration is regulated through SDF-1 and its receptor CXCR4. Studies have demonstrated endogenous mobilisation of different populations of stem and progenitor cells by administering growth factors with a pharmacological antagonist of CXCR4, AMD3100. This may therefore be a means to improve compromised fracture healing. A 1.5mm femoral osteotomy in adult female Wistar rats was stabilised with an external skeletal fixator. After osteotomy, saline/PBS (P) VEGF (V), IGF-1 (I) or GCSF (G) (100ug/kg, 0.5ml/100g i.p.), were administered daily for 4 days. On day 5, a single 5mg/kg i.p. dose of AMD3100 was given. Control group (C) did not receive growth factors or AMD 3100. At 5 weeks, the femur was retrieved and microCT scanned. Compared to group C (n=7), group P (n=5) had a significant increase in bone volume (P=0.01) 8.9±2.2um∧3 (control 4.3±3.1um∧3) and trabecular thickness (P=0.03). Group I (n=6) also had a significant increase in bone volume (P=0.035) 5.1±4.2um∧3 and trabecular thickness 0.062±0.008um (control 0.042±0.01um) (P=0.01). Group V (n=8), showed a non-significant increase in bone volume; 5.22±1.7um∧3 and trabecular thickness 0.048±0.007um. Group G (n=5) showed a significant decrease in bone volume (2.5±2.6um∧3) (P=0.048). AMD3100 alone and IgF1-AMD3100, showed the greatest increase in bone formation, presumably through mobilisation of beneficial combinations of stem and progenitor cells. GCSF-AMD3100, which is expected to mobilise hematopoietic progenitors inhibited bone healing.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_8 | Pages 5 - 5
1 May 2018
Calder P Koroma P Wright J Goodier D Taylor S Blunn G Moazen M
Full Access

Aim

To quantify the micro-motion at the fracture gap in a tibial fracture model stabilised with an external fixator.

Method

A surrogate model of a tibia and a cadaver leg were fractured and stabilised using a two-ring hexapod external fixator. They were tested initially under static loading and then subjected to vibration.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_9 | Pages 29 - 29
1 May 2018
Hothi H Eskelinen A Henckel J Blunn G Skinner J Hart A
Full Access

Introduction

Numerous studies have reported on clinically significant volumes of material loss and corrosion at the head-stem junction of metal-on-metal (MOM) hips; less is understood about metal-on-polyethylene (MOP) hips. We compared the effect of bearing type (MOM vs MOP) on taper material loss for a hip system of a single design (DePuy Pinnacle).

Methods

We recruited retrieved MOM (n=30) and MOP (n=22) bearing hips that were consecutively received at our centre.

We prospectively collected associated clinical and imaging data. We measured the severity of corrosion and volumes of material loss at each head taper surface and used multivariate statistical analysis to investigate differences between the two bearing types.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 289 - 297
1 Apr 2018
Sanghani-Kerai A Osagie-Clouard L Blunn G Coathup M

Objectives

This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis.

Methods

Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant.


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 455 - 460
1 Apr 2018
Mumith A Thomas M Shah Z Coathup M Blunn G

Increasing innovation in rapid prototyping (RP) and additive manufacturing (AM), also known as 3D printing, is bringing about major changes in translational surgical research.

This review describes the current position in the use of additive manufacturing in orthopaedic surgery.

Cite this article: Bone Joint J 2018;100-B:455-60.


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 271 - 284
1 Mar 2018
Hexter AT Thangarajah T Blunn G Haddad FS

Aims

The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR.

Materials and Methods

In all, 1879 studies were identified across three databases. Following assessment against strict criteria, 112 studies were included (20 clinical studies; 92 animal studies).


Bone & Joint Research
Vol. 6, Issue 6 | Pages 358 - 365
1 Jun 2017
Sanghani-Kerai A Coathup M Samazideh S Kalia P Silvio LD Idowu B Blunn G

Objectives

Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration.

Methods

MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_9 | Pages 75 - 75
1 May 2017
Koris J Blunn G Coathup M
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Background

Children suffering from primary bone cancer necessitating resection of growth plates, may suffer progressive leg length discrepancy, which can be attenuated with extendable prostheses. A serious complication is catastrophic implant failure. Over time, bone will remodel, altering the stress pattern in the implant. By using finite element analysis we can model different bone remodeling conditions to ascertain the effect that this will have on stress distribution and magnitude.

A finite element analysis was performed. Simplified computer generated models were designed of a cemented femoral Stanmore growing massive endoprosthesis. Three scenarios were designed, modelled on post-operative radiographs. Scenario 1 had a gap between the end of the femur and the implant collar, scenario 2 had no gap, but with no bone attachment into the collar, and scenario 3 had growth of the bone over the length of the collar with attachment. Physiological loading conditions were applied. The resultant stress in the implant for each scenario was measured, and compared to the strength of the material. Peak stresses were recorded at the stem-collar junction.

The maximum stress recorded in the implant in scenario 1 was 3104.2Mpa, compared to 1054.4Mpa in scenario 2, and 321.2Mpa in scenario 3.

Conclusions

Both accurate reduction and bone growth with attachment to the stem of a massive endoprosthesis will greatly reduce the resultant stress in the implant under loading conditions. The load is redistributed throughout the length of the bone. This may help to prevent catastrophic failure in the implant under loading conditions. Further investigations of patient findings are needed to ensure the model findings are verified.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 27 - 27
1 Apr 2017
Adesina T Ajami S Coathup M Blunn G
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Background

Stress shielding and wear induced aseptic loosening cause failure in arthroplasty surgery. To improve survivorship, the use of a low modulus, low wearing biomaterial may be a suitable alternative to hard bearing prostheses, such as cobalt chromium (CoCr). There has been considerable research interest in the use of polyetheretherketone (PEEK) based on observed clinical success especially in spinal surgery. This study investigated the wear performance of PEEK, carbon reinforced PEEK (CFR-PEEK) and acetal as bearing materials in an all polymer total knee arthroplasty (TKA) using a unidirectional pin on plate test.

Methods

The following material combinations were tested: PEEK vs. UHMWPE, CFR-PEEK vs. UHMWPE, PEEK vs. PEEK, CFR-PEEK vs. PEEK, CoCr vs. UHMWPE, PEEK vs. XLPE, CFR-PEEK vs. CFR-PEEK, PEEK vs. Acetal, Acetal vs. XLPE and CoCr vs. XLPE.Tribological couples tested (Pin vs. Plate) Using a previously validated modification of ASTM F732, 20mm diameter spherically ended pins with a radius of 25mm were articulated against 40mm diameter plates. A load of 1000N was applied to generate a contact stress of about 70MPa similar to contact stresses previously reported in the knee. The lubricant used was 25% newborn calf serum containing 0.3% sodium azide to retard bacteria growth and 20mM EDTA to prevent calcium deposition. Three repeats of pin on plate combinations (including 2 passive soak controls) were tested for 2 million cycles at a cycle frequency of 1Hz and a stroke length of 10 mm. Gravimetric wear was analysed every 250,000 cycles and results converted to volumetric wear using material density.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 42 - 42
1 Apr 2017
Thangarajah T Pendegrass C Shahbazi S Lambert S Alexander S Blunn G
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Background

Re-attachment of tendon to bone is challenging with surgical repair failing in up to 90% of cases. Poor biological healing is common and characterised by the formation of weak scar tissue. Previous work has demonstrated that decellularised allogenic demineralised bone matrix (DBM) regenerates a physiologic enthesis. Xenografts offer a more cost-effective option but concerns over their immunogenicity have been raised. We hypothesised that augmentation of a healing tendon-bone interface with DBM incorporated with autologous mesenchymal stem cells (MSCs) would result in improved function, and restoration of the native enthesis, with no difference between xenogenic and allogenic scaffolds.

Methods

Using an ovine model of tendon-bone retraction the patellar tendon was detached and a complete distal tendon defect measuring 1 cm was created. Suture anchors were used to reattach the shortened tendon and xenogenic DBM + MSCs (n=5) and allogenic DBM + MSCs (n=5) were used to bridge the defect. Functional recovery was assessed every 3 weeks and DBM incorporation into the tendon and its effect on enthesis regeneration was measured using histomorphometry.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 37 - 37
1 Apr 2017
Sanghani A Coathup M Samazideh S Kalia P Di Silvio L Blunn G
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Background

Osteoporosis and bone fractures lead to immobility, chronic pain and high patient care costs. Mesenchymal stem cells (MSCs) from postmenopausal women have a slower growth rate and osteogenic differentiation ability causing lower bone density and reduced fracture healing capacity compared to MSCs from premenopausal women. Cellular movement and relocalisation are necessary for many physiologic properties. Local MSCs from injured tissues and circulating MSCs are involved in fracture healing. Cytokines and chemokines such as SDF-1 and its receptor CXCR4 play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. This study investigated the effect of CXCR4 over-expression on the migration of MSCs from ovariectomised, normal and young rats.

Methods

MSCs were harvested from femora of young, normal and OVX rats, genetically modified to over-express CXCR4and put in a Boyden chamber to establish their migration towards SDF-1. This was compared to the non-transfected stem cells.


Aims

The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft-tissue complications associated with socket prostheses and by improving sensory feedback and function. It relies on the formation of a seal between the soft tissues and the implant and currently has a flange with drilled holes to promote dermal attachment. Despite this, infection remains a significant risk. This study explored alternative strategies to enhance soft-tissue integration.

Materials and Methods

The effect of ITAP pins with a fully porous titanium alloy flange with interconnected pores on soft-tissue integration was investigated. The flanges were coated with fibronectin-functionalised hydroxyapatite and silver coatings, which have been shown to have an antibacterial effect, while also promoting viable fibroblast growth in vitro. The ITAP pins were implanted along the length of ovine tibias, and histological assessment was undertaken four weeks post-operatively.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_4 | Pages 61 - 61
1 Feb 2017
Khan H Riva F Pressacco M Meswania J Panagiotidou A Coathup M Blunn G
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Background

Complications of metal-on-metal hip resurfacing, leading to implant failure, include femoral notching, neck fracture, and avascular necrosis. Revision arthroplasty options include femoral-only revision with a head, however mis-matching radial clearance could accelerate metal ion release. Alternatively, revision of a well-fixed acetabular component could lead to further bone loss, complicating revision surgery. We have developed a ceramic hip resurfacing system with a titanium-ceramic taper junction; taking advantage of the low frictional torque and wear rates that ceramic affords. Taking a revision scenario into account, the ceramic head has a deep female taper for the resurfacing stem, but also a superficial tapered rim. Should revision to this resurfacing be required, any femoral stem with a 12/14 taper can be implanted, onto which a dual taper adaptor is attached. The outer diameter of the taper adaptor then becomes the male taper for the superficial taper of the ceramic head; ultimately allowing retention of the acetabular component. In an in-vitro model, we have compared the fretting corrosion of this taper adaptor to existing revision taper options: a titanium-cobalt chrome (Ti-CoCr) taper junction, and a titanium-titanium sleeve-ceramic (Ti-Ti-Cer) taper junction.

Methods

To simulate gait, sinusoidal cyclical loads between 300N-2300N, at a frequency of 3Hz was applied to different neck offsets generating different bending moments and torques. Bending moment and frictional torque were tested separately. An electrochemical assessment using potentiostatic tests at an applied potential of 200mV, was used to measure the fretting current (μA) and current amplitude (μA). In a short term 1000 cycle test with bending moment, four neck lengths (short to x-long) were applied. For frictional torque, four increments of increasing torque (2-4-6-8Nm) were applied. In a long-term test using the taper adaptor, the combination of worst-case scenario of bending and torque were applied, and fretting currents measured every million cycles, up to 10 million cycles.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_4 | Pages 60 - 60
1 Feb 2017
Khan H Meswania J Riva F Pressacco M Panagiotidou A Coathup M Blunn G
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Background

Hip resurfacing has advantages for the young active patient with arthritis; maintaining a large range of motion, preserving bone stock, and reduced dislocation risk. However high serum metal ion levels with metal-on-metal resurfacing, and their clinical implications, has led to a decline in the use of hip resurfacing. Ceramic bearing surfaces display the lowest frictional torque and excellent wear rates. Recent developments have enabled large, strong ceramic materials to be used as resurfacing components. Any wear debris that is generated from these articulations is inert. However an all-ceramic hip resurfacing could be at risk of fracture at the head-stem junction. A new ceramic hip resurfacing system with a titanium-ceramic modular taper junction has been developed. The introduction of a taper introduces the potential for fretting corrosion; we sought to determine the extent of this in an in-vitro model, and compared this prosthesis to the conventional 12/14 titanium-cobalt chrome (Ti6Al4V-CoCr) taper junction.

Methods

To simulate the gait cycle, sinusoidal cyclical loads between 300N-2300N, at a frequency of 3Hz, were applied to different head-neck offsets generating different bending moments and torques. The effect of increasing the bending moment and frictional torque were tested separately. Furthermore, the resurfacing head was mounted in a fixture held with just the stem, thus representing complete bone resorption under the head. An electrochemical assessment using potentiostatic tests at an applied potential of 200mV, was used to measure the fretting current (μA) and current amplitude (μA). In a short-term 1000 cycle test, six neck lengths (short to xxx-long) of the Ti6Al4V-CoCr taper were compared to the standard neutral (concentric), and 3mm A/P offset stem options for the resurfacing design. To represent frictional torque, four increments of increasing torque (2-4-6-8Nm) were applied to both tapers. In a long term test with the resurfacing stem, the worst-case scenario of the eccentric offset option and 8Nm of torque were applied, and potentiostatic measurements were taken every million cycles, up to 10 million cycles.


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 276 - 282
1 Feb 2017
Mumith A Coathup M Chimutengwende-Gordon M Aston W Briggs T Blunn G

Aims

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses.

Materials and Methods

The two novel designs of porous SLS collars, one with small pores (Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared in an ovine tibial diaphyseal model. Osseointegration of these collars was compared with that of a clinically used solid, grooved design (G). At six months post-operatively, the ovine tibias were retrieved and underwent radiological and histological analysis.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 18 - 18
1 Jan 2017
Palanca M Cristofolini L Pani M Kinene E Blunn G Madi K Tozzi G
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DVC allowed measurements of displacement and strain distribution in bone through the comparison of two, or more, 3D images. Hence, it has a potential as a diagnostic tool in combination with clinical CT. Currently, traditional computed tomography (CT) allows for a detailed 3D analysis of hard tissues, but imaging in a weight-bearing condition is still limited. PedCAT-CT (Curvebeam, USA) emerged as a novel technology allowing, for the first time, 3D imaging under full-weight bearing (Richter, Zech et al. 2015). Specifically, a PedCAT-CT based DVC was employed to establish its reliability through the strain uncertainties produced on bone structure targets, preliminarily to any further clinical studies. In addition, a reverse engineering FE modeling was used to predict possible force associated to displacement errors from DVC.

Three porcine thoracic vertebrae were used as bone benchmark for the DVC (Palanca, Tozzi et al. 2016, Tozzi, Dall'Ara et al. 2016). The choice of using porcine vertebrae (in a CT designed for foot/ankle) was driven by availability, as well as similar dimensions to the calcaneus. Each vertebra was immersed in saline solution and scanned twice without any repositioning (zero-strain-test) with a pedCAT-CT (Curvebeam, USA) obtaining an isotropic voxel size of 370 micrometers. Volumes of interest of 35 voxel were cropped inside the vertebrae. Displacement and strains were evaluated using DVC (DaVis-DC, LaVision, Germany), with different spatial resolution. The displacement maps were used to predict the force uncertainties via FE (Ansys Mechanical v.14, Ansys Inc, Canonsburg, PA). Each element was assigned a linear elastic isotropic constitutive law (Young modulus: 8 GPa, Poisson's ratio: 0.3, as in (Follet, Peyrin et al. 2007)). Overall, the precision error of strain measurement was evaluated as the average of the standard deviation of the absolute value of the different component of strain (Liu and Morgan 2007).

The force uncertainties obtained with the FE analysis produced magnitudes ranging from 231 to 2376 N. No clear trend on the force was observed in relation to the spatial resolution. Precision errors were smaller than 1000 microstrain in all cases, with the lowest ranging from 83 microstrain for the largest spatial resolution. Full-field strain on the bone tissue did not seem to highlight a preferential distribution of error in the volume.

The precision errors showed that the pedCAT-CT based DVC can be sufficient to investigate the bone tissue failure (7000–10000 microstrain) or, physiological deformation if well-optimized. FE analysis produced important force uncertainties up to 2376 N. However, this is a preliminary investigation. Further investigation will give a clearer indication on DVC based PedCAT-CT, as well as force uncertainties predicted. So far, the DVC showed its ability to measure displacement and strain with reasonable reliability with clinical-CT as well.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 84 - 84
1 Jan 2017
Osagie L Sanghani-Kerai A Coathup M Briggs T Blunn G
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Intermittent parathyroid hormone 1–34 (teriparatide) is the N-fragment terminal of the intact hormone, currently in clinical use to treat osteoporosis. Unlike anti-catabolic agents such as bisphosphonates, PTH 1–34 not only affects the osteoclast, but also up regulates bone formation via both modelling and remodelling mechanisms. The actions of iPTH on mesenchymal stem cell differentiation (MSCs) may underpin a further method in the treatment of osteoporosis specifically, and for fracture healing in general. Stem cells from older female osteoporotic animals have reduced activity and poorer osteogenic potential; additionally, their migration to and retention at sites of increased bone turnover are reduced in comparison to cells from younger animals. The aim of this study was to isolate bone marrow derived MSCs from both young Wild Type (WT) and ovarectomized senile (OVX) rats, then to investigate and compare the effect of pulsatile and continuous PTH administration on migration to SDF-1, proliferation and osteogenic differentiation.

MSCs were harvested from the femora of 6–9week Wistar rats, and from 10–13month ovarectomized rats with established osteopenia. Cells were cultured with 25, 50 and 100nmMol of PTH 1–34 added to osteogenic media either continuously or in a pulsatile fashion for 6 hours in every 72hour cycle. ALP and Alizarin Red were used to assess the optimal concentration of PTH for osteogenic differentiation. Subsequently, proliferation was assessed with Alamar Blue and cells were seeded in a Boyden chamber to quantify the migration to SDF-1. As the data was parametric a student t-test was used to analyse results, and a p value < 0.05 was considered significant.

ALP and Alizarin Red parameters were significantly increased for both WT and OVX groups at 50nmMol of pulsatile PTH in comparison to groups cultured in 25 or 100nmMol. Continuous administration at all concentrations led to reduced calcium phosphate deposition by day 21 in all groups. Interestingly, in comparison to cells cultured in osteogenic media, 50nmMol of pulsatile PTH lead to statistically significant higher ALP and Alizarin Red measurements up to day 10 and 14 respectively in WT cells, and days 10 and 21 in OVX cells. The proliferation rate normalised against DNA was similar for both OVX and WT rats at all-time points. PTH administration did not effect cell proliferation in any group. WT MSCs not only had improved osteogenic differentiation, but also showed increased migration to SDF-1 in comparison to OVX groups. Pulsatile PTH led to further increases in migration of both OVX and WT cells.

Intermittent PTH increases the osteogenic diffrentiation and migration of MSCs from both young and ovarectomised rats, though importantly this effect is not dose dependent. Ultimately, the role of PTH 1–34 on MSCs may lead to improved bone formation and cell homing capacity-particularly in the context of osteoporosis.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 28 - 28
1 Jan 2017
Osagie L Sanghani-Kerai A Coathup M Briggs T Blunn G
Full Access

Osteoporosis is characterised by an uncoupling of bone formation and resorption resulting in a net reduction in bone density. Stem cells derived from bone marrow in osteoporotic patients typically contain more adipocytes,. Intermittent Parathyroid hormone (iPTH), has been shown to cause the preferential differentiation of mesenchymal stem cells (MSCs) to osteoblasts. We isolated rat bone marrow derived MSCs, investigating the effect of iPTH on adipocyte differentiation.

MSCs were harvested from the femora of 6–10week oldWT rats and cultured to induce adipogenesis for 21 days. Subsequently, cells were continually cultured in adipogenic media, osteogenic media or in osteogenic media supplemented with PTH 1–34 either continuously or intermittently for 6hours in every 72hour cycle. ALP and Alizarin Red assessed osteogenic differentiation, and Oil Red O used to assess intracellular microdroplet formation. A student t-test was used to analyse results, and a p value<0.05 considered significant.

Quantitatively measurements of Alizarin Red staining significantly increased in all adipocytes grown in osteogenic media compared to the cells continually cultured in adipogenic media. Calcium phosphate deposition continued to increase significantly in these groups up to day 14. At day 14, Alizarin Red staining from cells cultured in iPTH were significantly higher than osteogenic media alone. ALP expression was significantly higher for cells cultured in osteogenic media and iPTH compared to adipogenic media at days 3–14. Expression peaked at day 7, at this timepoint cells cultured in iPTH expressed significantly more ALP than other groups. Oil Red O measurements were significantly reduced from days 7–14 for all osteogenic groups, this significance was greatest for the iPTH group at day 7.

iPTH increased the transdifferentiation of adipocytes derived from MSCs into osteoblasts, this effect was most significant after 7 days. Ultimately, the role of iPTH on adipocytes may lead to improved bone formation with many orthopaedic applications.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 59 - 59
1 Jan 2017
Sanghani Kerai A Osagie L Coathup M Blunn G
Full Access

The current treatment for osteoporosis such as bisphosphonates inhibits the catabolic activity of osteoclasts and subsequent bone resorption, but does not increase bone formation. There is therefore interest in using anabolic factors such as stem cells to augment fracture repair. The poor bone formation in postmenopausal women could be due to poor retention and function of Mesenchymal stem cells (MSCs) resulting into delayed unions. Another factor associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities.

Ovariectomy was performed in 6–9 month old Wistar rats and osteopenia developed over a 4 month post-op period. MSCs were harvested from the femora of young, adult and osteopenic Wistar rats. Proliferation of the these MSCs from the three group of rats was measured using Alamar blue, osteogenic differentiation was measured using ALP expression at day 0, 7, 14 and 21 and alizarin red at day 21. Adipogenic differentiation was measured at day 7, 14 and 21 using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. For analysis, the number of cells migrating across the membrane was expressed as a percentage of the cells remaining on the upper membrane surface. Data was analysed using a Student t-test where p values < 0.05 were considered significant.

The stem cells from all 3 groups of rats expressed on average the same amount of CD29 (>90%), CD90 (>96%), CD34 (<5%) and CD45 (approx 10%). The proliferation rate measured by Alamar blue normalised against DNA was also similar at day 3, 7, 10 and 14. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat as well, but they also migrated significantly more towards SDF1. The migration of SDF-1 doubled with young rats compared to the adult rats (p = 0.023) and it was four times higher when compared to cells isolated from OVX rats (p = 0.013).

MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4).


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 81 - 81
1 Jan 2017
Cheng Y Samizadeh S Coathup M Blunn G
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Mesenchymal stem cells (MSCs) are believed to be immune-privileged due to lack of antigen-presenting-cell related markers, however, evidence suggests that MSCs are immunogenic and are attacked by the immune system. Our research investigates the hypothesis that there are differences between MSC clones from the same individual in terms of their morphology, proliferation, differentiation and immune profile. Our goal is to discover immune-privileged stem cells, which can act as a universal allogenic mesenchymal stem cell donor to facilitate bone ingrowth for osteosarcoma patients status post tumor excision and prosthesis implantation.

Serial dilutions of bone-marrow derived (BMMSCs) and adipose derived mesenchymal stem cells (ADMSCs) from same animal were carried out in order to isolate single-cell clones. From a single animal we obtained 3 clones from BMMSCs and 3 from ADMSCs. This procedure was repeated for another other 2 animals. The proliferation rate and cell doubling time of each clonal culture was measured. The proliferation rate of mixed clonal cultures was also measured. The tri-differentiation potential of the clonal cultures was compared and a comparison was also made with the original isolates from bone marrow and fat. The immune-privileged properties were measured by flow cytometry and immuno-staining for the major histocompatibility complex (MHC) antigens. To measure the immune response a mixed leucocyte reaction was used but where leucocytes from a different individual were mixed with the clonal MSC cells.

All isolates were able to differentiate into osteoblasts, chondrocytes and adipocytes. All clonal cultures revealed significantly different proliferation rates and doubling times when compared with each other and with mixed cultures. All clonal cultures showed different surface marker presentations, which included differences in the expression of MHC antigens. One clone isolated from ADMSCs showed lack of MHCI and MHCII. Our mixed leucocyte reaction and MHC staining showed variety of immune-modulation and this was related to the expression of the MHC antigens.

All clones tri-differentiated and therefore show a degree of ‘stemness’. MSCs are generally are believed not to express MHC II and to be immune-privileged. However, this study shows that the expression of these antigens in clones isolated from bone marrow and from fat is variable. A heterogeneous result indicates individual differences between MSCs, even from same origin. The immune response elicited by MSCs is complicated. MSCs have been shown to release interleukin 10, which could inhibit the immune response but on the other hand interferon-gamma could enhance MHCII presentation in some MSCs. Our results confirmed our hypothesis because clonal cultures isolated from different sources of MSCs in the same animal showed significant differences in proliferation rate, morphology and surface marker presentation. Mesenchymal stem cells are not immunogenic or immune-privileged. Individual differences highlighted through single-cell clonal cultures may be the key to finding a universal immune-privileged MSCs for allogeneic transplantation.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 14 - 21
1 Jan 2017
Osagie-Clouard L Sanghani A Coathup M Briggs T Bostrom M Blunn G

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.

Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 59 - 59
1 Dec 2016
Hislop S McKenna D Coathup MJ Blunn G Briggs T
Full Access

Aim

Photodynamic therapy (PDT) requires a photosensitiser, a light source of an appropriate wavelength, and the presence of molecular oxygen. Once stimulated to its excited phase by the light, the photosensitiser reacts with oxygen to form free radicals of ‘singlet oxygen’ which is cytotoxic to microorganisms.

We aim to demonstrate the effectiveness of PDT as an in-vitro antimicrobial technique against Staphylococcus aureus, Methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter bauminii. This will form the scientific basis for further animal and human studies assessing PDT for treatment of periprosthetic infections, septic arthritis, and open fractures.

Method

A PDT treatment protocol was devised using lawns of bacteria on agar plates. PDT was targeted towards the bacteria and the remaining microorganisms were quantified using a serial dilution technique. In order to assess the ability of photodynamic therapy to target biofilms on metallic implants, biofilms were cultured on polished titanium and hydroxyapatite-coated titanium discs and subjected to PDT.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 2 - 2
1 Oct 2016
Clouard L Sanghani-Kerai A Coathup M Briggs T Blunn G
Full Access

Osteoporosis is characterised by an uncoupling of bone formation and resorption resulting in net resorption. Stem cells derived from bone marrow in osteoporotic patients typically contain more adipocytes. Intermittent Parathyroid hormone (iPTH), has been shown to cause the preferential differentiation of mesenchymal stem cells (MSCs) to osteoblasts. We isolated rat bone marrow derived MSCs, investigating the effect of iPTH on adipocyte differentiation.

MSCs were harvested from the femora of 6–10week oldWT rats and cultured to induce adipogenesis for 21 days. Subsequently, cells were continually cultured in adipogenic media, osteogenic media or in osteogenic media supplemented with PTH 1–34 either continuously or intermittently for 6hours in every 72hour cycle. ALP and Alizarin Red assessed osteogenic differentiation, and Oil Red O used to assess intracellular microdroplet formation. A student t-test was used to analyse results, and a p value<0.05 considered significant.

Quantitatively measurements of Alizarin Red staining significantly increased in all adipocytes grown in osteogenic media compared to the cells continually cultured in adipogenic media. Calcium phosphate deposition continued to increase significantly in these groups up to day 14. At day 14, Alizarin Red staining from cells cultured in iPTH were significantly higher than osteogenic media alone.

ALP expression was significantly higher for cells cultured in osteogenic media and iPTH compared to adipogenic media at days 3–14. Expression peaked at day 7, at this timepoint cells cultured in iPTH expressed significantly more ALP than other groups (Figure 2). Oil Red O measurements were significantly reduced from days 7–14 for all osteogenic groups, this significance was greatest for the iPTH group at day 7.

iPTH increased the transdifferentiation of adipocytes derived from MSCs into osteoblasts, this effect was most significant after 7 days. Ultimately, the role of iPTH on adipocytes may lead to improved bone formation with many orthopaedic applications.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 4 - 4
1 Oct 2016
Cheng Y Sorousheh S Coathup M Blunn G
Full Access

Mesenchymal stem cells (MSCs) are usually believed to be immune-privileged. However, immunogenic MSCs were also reported. We hypothesize that there are differences between MSC clones from the same individual in terms of their morphology, proliferation, differentiation and immunogenicity. Our goal is to discover immune-privileged stem cells for universal allogenic MSCs transplantation.

Serial dilutions of bone-marrow derived (BMMSCs) and adipose derived mesenchymal stem cells (ADMSCs) from same animal were carried out to isolate single-cell clones. From a single animal we obtained 3 clones from BMMSCs and 3 from ADMSCs. The proliferation rate of each clonal culture and mixed clonal culture were measured. The tri-differentiation potential of the clonal cultures was compared, as well as with the original isolates from bone marrow and fat. The immune-privileged properties were measured by flow cytometry and immuno-staining for the major histocompatibility complex (MHC) antigens. Mixed leucocyte reaction (MLR) were also performed to investigate immunogenicity.

Tri-differentiation was confirmed in all isolates. All clonal cultures revealed significant different morphology and proliferation rates, compared with each other and mixed cultures. All clonal cultures showed different surface markers, inclusive of MHC antigens. One clone from ADMSCs showed lack of MHC antigens. Our MLR and MHC staining disclosed variety of immune properties.

All clones tri-differentiated which indicated a degree of ‘stemness’. MSCs are generally believed not to express MHC II, resulting in immune-privileged. Our results confirmed our hypothesis because clonal cultures isolated from different origins of same animal show differences in morphology, proliferation rate, and surface marker presentation. Individual immune differences highlighted through single-cell clonal cultures may be crucial to find universal immune-privileged MSCs as universal allogeneic donor.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 50 - 50
1 Oct 2016
Clouard L Sanghani-Kerai A Coathup M Briggs T Blunn G
Full Access

Intermittent parathyroid hormone (iPTH 1–34) increases bone formation via modelling and remodelling mechanisms and as such is used to treat osteoporosis. The actions of iPTH on mesenchymal stem cell (MSCs) may underpin a further treatment option.

We isolated bone marrow derived MSCs from young (WT) and ovarectomized senile (OVX) rats, investigating the effect of intermittent and continuous PTH administration on migration to SDF-1, proliferation and osteogenic differentiation.

MSCs were harvested from the femora of 6–10week old WT rats and 10–13month old OVX rats. Cells were cultured with 25,50 and 100nmMol of PTH 1–34 added to osteogenic media either continuously or intermittently for 6hours in every 72hour cycle. ALP and Alizarin Red assessed osteogenic differentiation, and Alamar Blue- proliferation. Cells were seeded in a Boyden chamber to quantify SDF-1 migration. A student t-test was used to analyse results, and a p value<0.05 considered significant.

ALP and Alizarin Red were significantly increased for WT and OVX groups at 50nmMol of iPTH. Continuous administration at all concentrations reduced calcium phosphate deposition by day 21 in all groups.

In comparison to cells cultured in osteogenic media, 50nmMol of iPTH led to significantly higher ALP and Alizarin Red measurements up to days 10 and 7 respectively (figure 1). There was no change in proliferation between the groups, and PTH had no effect (figure 2.)

WT MSCs not only had improved osteogenic differentiation, but also showed increased migration to SDF-1 in comparison to OVX groups. iPTH led to further increases in migration of both OVX and WT cells.

iPTH increases the osteogenic differentiation and migration of MSCs from both young and ovarectomised rats, though this effect is not dose dependent. Ultimately, the role of iPTH on MSCs may lead to improved bone formation and cell homing capacity-particularly in the context of osteoporosis.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_16 | Pages 49 - 49
1 Oct 2016
Kerai AS Coathup M Osagie L Samizadeh S Blunn G
Full Access

There is increasing interest in using anabolic factors such as stem cells to augment fragility fracture repair. One of the factors associated with fracture healing is the retention and migration of stem cells to the site of injury (1–3). The aim of this study was to isolate stem cells from osteopenic rats and investigate and compare the CD marker expression, proliferation, migration, osteogenic and adipogenic differentiation. The hypothesis of this study is that the migration of MSCs from young, adult and ovariectomised (OVX) rats will have different proliferation, differentiation and migratory abilities.

CD marker expression of MSCs from young, adult and osteopenic rats was measured using flow cytometry. Proliferation, osteogenic differentiation and adipogenic differentiation was measured using Alamar Blue, ALP expression and Alizari n Red and quantitative Oil red O respectively. Cells were incubated in Boyden chambers to quantify their migration towards SDF1. Data was analysed using a Student t-test where p values < 0.05 were considered significant.

MSCs from all 3 groups of rats had similar proliferation and expression of CD29(>90%), CD90(>96%), CD34(<5%) and CD45(approx 10%). The proliferation rate was also similar. However, interestingly the migration and differentiation ability was significantly different between the MSCs from the 3 groups of rats. The young MSCs were not only better at differentiating into bone and fat, but they also migrated significantly more towards SDF1. MSCs from OVX rats are similar to MSCs from young rats. However when induced to turn into bone, fat and migrate towards SDF1, young MSCs are significantly more responsive than MSCs from OVX and adult control rats. The poor homing ability and differentiation of the stem cells and their retention may result in a reduction in bone formation leading to delayed union in fractures of osteoporotic patients(4).


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_9 | Pages 83 - 83
1 May 2016
Christiansen J Nielsen P Laursen M Blunn G
Full Access

Introduction

The Primoris® femoral stem was designed to preserve bone and maintain normal stress to the proximal femur, thereby minimizing stress-shielding. The implant is anchored in the femoral neck and metaphysis without diaphysial involvement and differs from other neck prothesis by: a) Elliptical shape to fit the inner neck dimensions. b) On top of Ti– porous-coating electrochemically deposited hydroxy apatite (Bonemaster®) c) The surgical technique aims to enhance initial implant stability by compaction of neck and metaphyseal cancellous bone.

Objectives

As part of stepwise introduction to monitor bone remodeling, RSA data and clinical results.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 8 - 8
1 May 2016
Adesina T Ajami S Coathup M Blunn G
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Introduction

Stress shielding and wear induced aseptic loosening cause failure in total joint arthroplasty. To improve long-term outcomes in total knee arthroplasty (TKA), the use of a low modulus, low wearing biomaterial may be a suitable alternative to cobalt chromium (CoCr) femoral components. Based on its favorable mechanical properties and observed clinical success especially in spinal surgery, polyetheretherketone (PEEK) is investigated as a candidate material for a metal free TKA. An all polymer TKA has several theoretical advantages, these include a more physiological stress in the distal femur, elimination of biological reaction to metal, better radiographic visualisation of the bone implant interface especially with CT and MRI. In addition, polymers afford a cheaper option for the manufacture of prostheses.

Aims and Hypothesis

This study investigated the wear performance of PEEK and carbon reinforced PEEK (CFR-PEEK) as bearing materials in an all polymer TKA using a unidirectional pin on plate test. Our hypothesis was that reduced wear is generated from PEEK or CFR-PEEK bearings when compared with metal on polyethylene (MoP) bearings and that this combination may provide a suitable alternative in TKA.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 10 - 10
1 May 2016
Ajami S Coathup M Khoury J Blunn G
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Background

Polyetheretherketone (PEEK) may be advantageous as an alternative material to metal alloys in some orthopaedic applications. However, it is bioinert and does not osseointegrate1. A novel accelerated neutral atom beam technique (ANAB) has been developed to improve the bioactivity of PEEK where the surface is modified to a depth of 5 nm without affecting the integrity of the underlying PEEK structure2.

Aim

The aim of this study was to investigate the growth of human Mesenchymal Stem Cells (hMSCs), adult human Osteoblasts (hOB) and skin Fibroblasts (BR3G) on PEEK and ANAB treated PEEK.


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 579 - 584
1 May 2016
Osman K Panagiotidou AP Khan M Blunn G Haddad FS

There is increasing global awareness of adverse reactions to metal debris and elevated serum metal ion concentrations following the use of second generation metal-on-metal total hip arthroplasties. The high incidence of these complications can be largely attributed to corrosion at the head-neck interface. Severe corrosion of the taper is identified most commonly in association with larger diameter femoral heads. However, there is emerging evidence of varying levels of corrosion observed in retrieved components with smaller diameter femoral heads. This same mechanism of galvanic and mechanically-assisted crevice corrosion has been observed in metal-on-polyethylene and ceramic components, suggesting an inherent biomechanical problem with current designs of the head-neck interface.

We provide a review of the fundamental questions and answers clinicians and researchers must understand regarding corrosion of the taper, and its relevance to current orthopaedic practice.

Cite this article: Bone Joint J 2016;98-B:579–84.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_12 | Pages 4 - 4
1 Nov 2015
Osman K Panagiotidou A Meswania J Skinner J Hart A Haddad F Blunn G
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Introduction

Recent studies on large diameter femoral head hip replacements have implicated the modular taper junction as one of the significant sources of wear and corrosion products and this has been attributed to increased torque and bending on the taper interface. The aim of this study was to assess the effect of frictional torque and bending moment on fretting corrosion at the taper junction and to investigate whether different material combinations also had an effect.

Patients/Materials & Methods

We examined 1) Cobalt Chromium (CoCr) heads on CoCr stems 2) CoCr heads on Titanium alloy (Ti) stems and 3) Ceramic heads on CoCr stems. In test 1 increasing torque was imposed by offsetting the femoral stem in the anterior posterior plane in increments of 0 mm, 4 mm, 6 mm and 8 mm where the force generated was equivalent to 0Nm, 9Nm, 14Nm and 18Nm. In Test 2 we investigated the effect of increasing bending moment by offsetting the application of axial load from the midline in the medial-lateral (ML). Offset increments equivalent to +0, +7 and +14 heads were used. For each test we used n=3 for each different material combination.


The Bone & Joint Journal
Vol. 97-B, Issue 4 | Pages 463 - 472
1 Apr 2015
Panagiotidou A Meswania J Osman K Bolland B Latham J Skinner J Haddad FS Hart A Blunn G

The aim of this study was to assess the effect of frictional torque and bending moment on fretting corrosion at the taper interface of a modular femoral component and to investigate whether different combinations of material also had an effect. The combinations we examined were 1) cobalt–chromium (CoCr) heads on CoCr stems 2) CoCr heads on titanium alloy (Ti) stems and 3) ceramic heads on CoCr stems.

In test 1 increasing torque was imposed by offsetting the stem in the anteroposterior plane in increments of 0 mm, 4 mm, 6 mm and 8 mm when the torque generated was equivalent to 0 Nm, 9 Nm, 14 Nm and 18 Nm.

In test 2 we investigated the effect of increasing the bending moment by offsetting the application of axial load from the midline in the mediolateral plane. Increments of offset equivalent to head + 0 mm, head + 7 mm and head + 14 mm were used.

Significantly higher currents and amplitudes were seen with increasing torque for all combinations of material. However, Ti stems showed the highest corrosion currents. Increased bending moments associated with using larger offset heads produced more corrosion: Ti stems generally performed worse than CoCr stems. Using ceramic heads did not prevent corrosion, but reduced it significantly in all loading configurations.

Cite this article: Bone Joint J 2015;97-B:463–72.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 10 - 18
1 Jan 2015
Sabah SA Henckel J Cook E Whittaker R Hothi H Pappas Y Blunn G Skinner JA Hart AJ

Arthroplasty registries are important for the surveillance of joint replacements and the evaluation of outcome. Independent validation of registry data ensures high quality. The ability for orthopaedic implant retrieval centres to validate registry data is not known. We analysed data from the National Joint Registry for England, Wales and Northern Ireland (NJR) for primary metal-on-metal hip arthroplasties performed between 2003 and 2013. Records were linked to the London Implant Retrieval Centre (RC) for validation. A total of 67 045 procedures on the NJR and 782 revised pairs of components from the RC were included. We were able to link 476 procedures (60.9%) recorded with the RC to the NJR successfully. However, 306 procedures (39.1%) could not be linked. The outcome recorded by the NJR (as either revised, unrevised or death) for a primary procedure was incorrect in 79 linked cases (16.6%). The rate of registry-retrieval linkage and correct assignment of outcome code improved over time. The rates of error for component reference numbers on the NJR were as follows: femoral head category number 14/229 (5.0%); femoral head batch number 13/232 (5.3%); acetabular component category number 2/293 (0.7%) and acetabular component batch number 24/347 (6.5%).

Registry-retrieval linkage provided a novel means for the validation of data, particularly for component fields. This study suggests that NJR reports may underestimate rates of revision for many types of metal-on-metal hip replacement. This is topical given the increasing scope for NJR data. We recommend a system for continuous independent evaluation of the quality and validity of NJR data.

Cite this article: Bone Joint J 2015;97-B:10–18.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 158 - 158
1 Jul 2014
Elnikety S Pendegrass C Holden C Blunn G
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Summary

Our results prove that Demineralised Cortical Bone (DCB) can be used as biological tendon graft substitute, combined with correct surgical technique and the use of suture bone anchor early mobilisation can be achieved.

Introduction

Surgical repair of tendon injuries aims to restore length, mechanical strength and function. In severe injuries with loss of tendon substance a tendon graft or a substitute is usually used to restore functional length. This is usually associated with donor site morbidity, host tissue reactions and lack of remodelling of the synthetic substitutes which may result in suboptimal outcome. In this study we hypothesise that DCB present in biological tendon environment with early mobilisation and appropriate tension will result in remodelling of the DCB into ligament tissue rather that ossification of the DCB at traditional expected. Our preparatory cadaveric study (abstract submitted to CORS 2013) showed that the repair model used in this animal study has sufficient mechanical strength needed for this animal study.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 45 - 45
1 Jul 2014
Vanhegan I Coathup M McCarthy I Haddad F Blunn G
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Summary Statement

Proximal femoral bony deficits present a surgical and biomechanical challenge to implant longevity in revision hip arthroplasty. This work finds comparable primary stability when a distally fixing tapered fluted stem was compared with a conical design in cadaveric tests.

Introduction

Proximal bony deficits complicate revision hip surgery and compromise implant survival. Longer distally fixing stems which bypass such defects are therefore required to achieve stability compatible with bony ingrowth and implant longevity.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 159 - 159
1 Jul 2014
Elnikety S Pendegrass C Alexander S Blunn G
Full Access

Summary

Our study shows that a tendon rupture can be successfully augmented with Demineralised Cortical Bone (DCB) giving initial appropriate mechanical strength suitable for in vivo use providing the biological reactions to the graft are favourable.

Introduction

Treatment of tendon and ligament injuries remains challenging; the aim is to find a biocompatible substance with mechanical and structural properties that replicate those of normal tendon and ligament. Because of its structural and mechanical properties, we proposed that DCB can be used in repair of tendon and ligament as well as regeneration of the enthesis. DCB is porous, biocompatible and has the potential to be remodelled by the host tissues. 2 studies were designed; in the first we examined the mechanical properties of DCB after gamma irradiation (GI) and freeze drying (FD). In the second we used different techniques for repairing bone-tendon-bone with DCB in order to measure the mechanical performance of the construct.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 91 - 91
1 Jul 2014
Dowling R Pendegrass C Thomas B Blunn G
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Summary

Osseointegrated Amputation Prostheses can be functionalised by both biological augmentation and structural augmentation. These augmentation techniques may aid the formation of a stable skin-implant interface.

Introduction

Current clinical options are limited in restoring function to amputees, and are associated with contact dermatitis and infection at the stump-socket interface. Osseointegrated Amputation Prosthesis attempts to solve issues at the stump-socket interface by directly transferring axial load to the prosthesis, via a skin-penetrating abutment. However, development is needed to achieve a seal at the skin-implant interface to limit infection. Fibronectin, an Extracellular Matrix protein, binds to integrins during wound healing, with the RGD tripeptide being part of the recognition sequence for its integrin binding domain. In vitro work has found silanization of RGD to polished titanium discs up regulates fibroblast attachment compared to polished control. Electron Beam Melting can produce porous titanium alloy implants, which may encourage tissue attachment. This study aims to test whether a combination of biological RGD coatings and porous metal manufacturing techniques can encourage the formation of a seal at the skin-implant interface.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_6 | Pages 19 - 19
1 Apr 2014
Yoon W Panagiotidou A Noordeen H Blunn G
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Aim:

The aim of this study was test the amount of corrosion occurring at the (Ti) /cobalt chrome (CoCr) interface comparing this with Ti and Ti interfaces. This was compared with retrieved metal work visualised under a scanning electron microscope (SEM).

Methods:

The interface of interest is the interface between rod and the screw. We investigated corrosion seen at that interface with a CoCr rod coupled to a Ti screw versus a Ti rod coupled to a Ti screw (6 screws were used) Implants were loaded according to the ASTM F2193 – 02 Standard Specifications and Test Methods for Components Used in the Surgical Fixation of the Spinal Skeletal System. Pitting potentials were monitored using cyclic potentiodynamic polarization tests (ASTM F2129 – 08 Standard Test Method for Conducting Cyclic Potentiodynamic Polarisation Measurements) to determine corrosion susceptibility. Retrieved implants were visualised under (SEM) to confirm corrosion.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_6 | Pages 15 - 15
1 Apr 2014
Lukina E Blunn G Kollero M Meswania J Mason P Wagstaff P Laka A Noordeen H Yoon W
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Introduction:

Due to absence of fusion in guided-growth devices for EOS (growing rods, Shilla, LSZ) movement of the rods against their attachment is possible resulting in wear debris formation. It is important to understand the wear resistance of materials used in these devices under appropriate conditions.

Aim:

The aim of our work was to investigate wear resistance of titanium alloy Ti-6Al-4V and superelastic Nitinol. Nitinol has been used recently for correcting scoliosis and may provide a better and more gradual correction than other materials.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 474 - 474
1 Dec 2013
Panagiotidou A Meswania J Hua J Muirhead-Allwood SK Skinner JA Hart A Blunn G
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Introduction:

There has been widespread concern regarding the adverse tissue reactions after metal-on-metal (MoM) total hip replacements (THR). Concerns have also been expressed with mechanical wear from micromotion and fretting corrosion at the head/stem taper junction in total hip replacements. In order to understand the interface mechanism a study was undertaken in order to investigate the effect of surface finish and contact area associated with modular tapers in total hip replacements with a single combination of materials of modular tapers.

Methods:

An inverted hip replacement setup was used (ASTM F1875-98). 28 mm Cobalt Chrome (CoCr) femoral heads were coupled with either full length (standard) or reduced length (mini) 12/14 Titanium (Ti) stem tapers. These Ti stem tapers had either a rough or smooth surface finish whilst all the head tapers had a smooth surface finish. Wear and corrosion of taper surfaces were compared after samples were sinusoidally loaded between 0.1 kN and 3.1 kN for 10 million cycles at 4 Hz. In test 1 rough mini stem tapers were compared with rough standard stem tapers whilst in test 2 rough mini stem tapers were compared with smooth mini stem tapers. Surface parameters and profiles were measured before and after testing. Electrochemical static and dynamic corrosion tests were performed between rough mini stem tapers and smooth mini stem tapers under loaded and non-loaded conditions.