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Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 289 - 289
1 May 2009
Middleton C Pendegrass C Gordon D Jacob J Blunn G
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Introduction: Cell adhesion to titanium alloy implants is important in osseointegration [1,2] and attachment of the soft tissues to skin penetrating implants e.g. external fixator pins and Intraosseous Transcutaneous Amputation Prostheses [3,4]. Cell adhesion can be assessed using cell area data and immunolocalisation of focal contact proteins e.g. vinculin; however no method of assessing biophysical attachment is performed routinely. Cell adhesion can be enhanced with adhesion proteins including fibronectin (Fn)[5]. We have previously shown that covalently binding Fn to titanium also increases cell adhesion, and produces a more robust protein coating [6]. However the strength of adhesion of cells to this coating has not been measured. Our hypothesis was that biophysical cell adhesion measured using novel radial flow apparatus would correlate with cell area and focal contact data and that covalently bound fibronectin substrates would increase cell adhesion compared with adsorbed and uncoated controls.

Method: Dermal fibroblasts were cultured for 1, 4, and 24 hours on 30mm and 10mm diameter polished titanium alloy discs (n = 6). Cells on 30mm discs were calcein stained and subjected to shear stress in a submerged, media filled, custom-made radial flow apparatus at 37¬C at 1.66ml/s for 15s. Cells were fixed in 10% formal saline and photographs were taken using a tangential light source. Fluorescent microscopy was performed at 2mm intervals along two perpendicular diameters. Using image analysis, the central cell free zone was measured and radial distance and shear stress calculated. Cells on 10mm discs were fixed, permeablised and vinculin stained (mouse vinculin antibody (1:200) 2hrs; FITC mouse antibody (1:100)1hr). Images were analyzed with a Zeiss microscope linked to image analysis software and the number of focal contacts were counted per cell area. The medians of the radial flow data were compared with data for cell area and focal contact production at the same time points using Spearman¡s regression correlation. This method was subsequently used to compare cell adhesion at one hour with adsorbed and covalently bound Fn substrates (10¥ìg/disc).

Results/Discussion: The shear strength of cells increased between 4 and 24hrs (p=0.002) on polished untreated control substrates. Attachment values (dynes/cm2) were 84.90 (73.98–97.19), 96.30 (91.66–100.89), and 136.69 (134.68–140.30) for 1, 4 and 24 hours respectively. At 1hr, covalently bound Fn (509.90 dynes/cm2 (490.55–528.49) significantly increased cell adhesion compared with adsorbed Fn(434.45 dynes/cm2(385.25–465.62)) and control substrates(p=0.002). There was significant correlation between shear stress and focal contacts/cell (1.00(p< 0.01)) and focal contacts/cell area (0.900(p=0.037)), but not cell area (0.600(p=0.285)).

Conclusion: Radial flow measurement is a useful direct method to quantify cell adhesion to orthopaedic implants and correlates well with other methods of measurement. Covalently bound Fn significantly increases biophysical cell attachment compared with adsorbed and uncoated controls.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 295 - 295
1 May 2009
Samizadeh S Coathup M Amogbokpa J Fang S Hing K Buckland T Blunn G
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Introduction: Incorporation of Silicon into the HA structure enhances the bioactivity of Hydroxyapatite (HA). Silicon substituted calcium phosphate (SiCaP/SiHA) has been introduced as an osteoconductive material for bone formation. However, the osseoinductive capacity of this biomaterial has not been assessed. A previous study by Hing et al shows that bioactivity of stoichiometric hydroxyapatite bone substitute materials is enhanced by increasing the level of porosity within the implant struts [1].

The aim of this study was to test the hypothesis that SiCaP bone graft results in superior osseoinduction compared to stoichiometric HA and osseoinduction enhancement using high microporosity materials.

Methods: Implantation of 32 bone graft plugs (16 granular and 16 blocks) with 3 different strut porosities: 20% SiHA, 35% SiHA, 10% SiHA and 20% HA, all with matched 80% total porosity supplied by ApaTech Ltd into the paraspinalis muscle of 4 sheep for 12 weeks. HA and %SiHA locations were randomized at implant sites.

Following euthanasia at 12 weeks histomorphometry was carried out to calculate Percentage of bone, soft tissue and implant area and Percentage of the amount of bone in contact with the calcium phosphate surface (% Bone attachment). Further evaluation of Calcium, Phosphate and Silicon levels within the implants and surrounding bone was carried out by Scanning Electron Microscopy (SEM) and EDAX.

Results: Bone formation was observed within the pores of both granules and blocks of SiCaP and HA implants. Greater bone formation and attachment was detected in scaffolds with higher strut porosity (SiHA35) compared to implants of the same chemical composition but lower strut porosity (SiHA10, SiHA20. More bone formation and contact was observed in SiHA implants (SiHA20) compared to matched porosity HA implants where the amount of bone formed was minimal. Uniform distribution of Silicon (Si) was visible within the SiHA scaffold struts according to EDAX results. Greater quantities of Si existed in newly formed bone as compared to soft tissue adjacent to the SiHA implants. Silicon was not detected in either soft or hard tissues adjacent to HA implants.

Conclusion: Both microporous HA and SiCaP promote bone ingrowth, as ectopic bone formation was observed in all four groups of synthetic materials. Matched porosity SiCaP is more osseoinductive than HA. Increasing strut porosity results in promotion of osseoinductivity. High strut porosity (> 10%) block environment contributes to greater osseoinductive behaviour. In conclusion we report that presence of silicon and the strut porosity influence the osseoinductive capacity of calcium phosphate bone substitute biomaterials.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 290 - 290
1 May 2009
Caruana J Janssen D Verdonschot N Hua J Blunn G
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Introduction: Finite element (FE) simulation of damage accumulation in the femoral cement mantle is widely used to predict failure of hip prostheses. It is often assumed that the stem-cement interface remains bonded, although debonding is thought to affect cement stress and damage. Rough stems may reduce subsidence, but have been reported to have a detrimental effect on implant survival. Other factors thought to influence cement damage include stem design and orientation and cement thickness. This study investigates the effect of cement mantle thickness and stem malpositioning on cement damage around a smooth, collared implant, and the extent to which this is affected by debonding of the stem-cement interface.

Method: Three FE meshes were built to represent proximal femora with Stanmore Hip prostheses implanted into a thick (2.5 mm) and a thin (1.0 mm) cement mantle, and another thin (1.0 mm) mantle with the implant tilted in varus to achieve a minimal thickness of 0.1 mm laterally. Each model consisted of 4304 eight-noded brick elements with frictional contact at the stem-cement interface. Two analyses were run for each model, in which the stem-cement interface was (a) fully bonded, and (b) fully debonded, with Coulomb frictional contact using a friction coefficient of 0.5. Standardised femur geometry and elastic properties were used. Creep and non-linear damage accumulation in the cement mantle under cyclic loading was modelled using subroutines developed by Stolk et al. (2003). Boundary conditions were applied representing a peak stair-climbing load.

Results: Bonded cases showed extensive cracking around the tip in all cases. Debonded cases had 4–8 times less cracking, which was much more focused at the tip; only the poorly-centralised mantle showed extensive damage elsewhere, in the very thin lateral region. When bonded, the thick mantle had least cracks and the poorly-centralised mantle had most; in the debonded cases, there was no major difference between thick, thin, and poorly-centralised mantles. For each cement mantle geometry, peak maximum principal cement stress was consistently lower in the debonded case than in the bonded case.

Discussion: Our results show greater, more widely distributed cracking in bonded than debonded cement mantles, in contrast with previous studies involving collarless implants. For a collared stem, calcar contact prevents subsidence, allowing cement stress relaxation. A possible explanation for our result is that debonding enhances the stress relaxation process, reducing and redistributing interfacial and shear stresses; thus reducing damage rates. In contrast, a debonded collarless stem subsides continuously, sustaining high cement stress levels and damage rates. These results may explain the disappointing clinical performance of some rough-surfaced prostheses. Our results suggest that bonding might increase both cement damage and its sensitivity to cement thickness. Similar results for all debonded cement mantles indicate that cement thickness may be less critical than previously thought for smooth, collared prostheses. Bonding should not be assumed in FE studies of smooth stems which clinically are likely to debond; cement damage simulation should be extended to incorporate the debonding process.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 288 - 288
1 May 2009
Kalia P Oussedik S Konan S Dodd M Coathup M Blunn G
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Introduction: Aseptic loosening at the bone-implant interface of THA acetabular components is a significant cause of implant failure. This loosening has been attributed either to wear particle-induced osteolysis or to the effects of joint fluid-pressure. It may be possible to prevent the loosening of implants by improving fixation between the bone and implant, or promoting the growth of a biological bony seal, in order to prevent the influx of wear particles or pressurized joint fluid. Additionally in revision implants it is important to promote osseointegration in situations where bone stock may be limited. The hypothesis of this study was spraying autologous BMSCs in fibrin glue onto the surface of HA-coated acetabular components would increase bone formation around the implant and improve bone-implant contact.

Materials and Methods: Bone marrow was aspirated from the iliac crest of six goats, and BMSCs isolated and expanded in vitro. 10 x 10e6 BMSCs were suspended in reconstituted thrombin pre-operatively. A standard posterior approach was used. The acetabular shell was then coated with 2 ml of fibrin glue, with (n=6) or without 10 x 10e6 autologous BMSCs (n=6), and the acetabular component impacted into position. Antibiotic and analgesic prophylaxes were carried out. All animals were weight bearing within 48 hours post-operatively. Walking and ground reaction forces were assessed pre-operatively, as well as 6 and 12 weeks post-operatively. Results were expressed as a percentage of force transmitted through the right leg versus the left leg. After 12 weeks, the acetabulae were retrieved, and processed for histology. The percentage of new bone around the cups was measured within 5 radial zones, using image analysis. Bone-implant contact was also analysed between the new bone and implant surface. Mann Whitney U test was used to show statistical significance.

Results: New bone formation in Zone 5 showed a significant increase in the BMSC group (71.97±10.91%), when compared to the controls (23.85±15.13%, p=0.028). The other zones did not show a significant difference. Overall new bone growth in the BMSC group was 30% greater than the control group (71.42±8.97% and 54.22±16.56%, respectively, p=0.58). Bone-implant contact was significantly improved in the BMSC group (20.03±4.64%), in contrast to the control group (13.71±8.32%, p=0.027). With regards to the force plate analysis, there was no significant difference in loading between groups at both 6 weeks (Controls-79.74±3.63%, BMSCs-59.39±9.33%, p=0.086) and 12 weeks (Controls-86.0%±2.85%, BMSCs-62.33±5.12%, p=0.055).

Discussion and Conclusions: In this study, overall bone growth was greater when cups were treated with BMSCs. Bone-implant contact was significantly improved as well. This study has clinical applications, as using MSCs in fibrin glue promotes a bony seal in contact with the implant which may prevent the migration of particles, or joint fluid, decreasing the likelihood of aseptic loosening of THAs, and improving their longevity. Also, this technique may improve fixation in situations where bone stock is reduced.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 289 - 289
1 May 2009
Mirza SB Greenwood M Blunn G
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Introduction There are 1 million cases of major skeletal defects :that occur worldwide each year that lead to significant morbidity and disability and currently require bone grafting as the main mode of treatment. Limitations of bone-grafting include donor site morbidity, reduced osseoinductivity and risk of pathogen transmission to the host. There is considerable interest in finding ways of differentiating mesenchymal stem cells down the osteoblastic lineage to form bone tissue. We hypothesized that there is an optimum strain that promotes differentiation of mesenchymal stem cells into osteoblasts.

Methods: A bioreactor was developed that was capable of applying tensional forces across a culture strip in a graduated manner within a range of 1-4373me. Mesenchymal stem cells were grown on these strips and subjected to cyclical tensile strain at 1Hz. Cell morphology using Scanning Electron Microscopy, mineralization using specialized stains and expression of core binding factor1 (Cbfa1) was studied at various strain levels.

Results: Scanning Electron Microscopy revealed classic osteoblastic cells in the regions subjected to tensile force, especially in the region where average strain was 1312me. X-ray microanalysis revealed calcium deposits on the strip, indicating osteoblastic differentiation. Cbfa1 expression was greatest in the region with an average strain 1312 me followed by a region on the strip subjected to just fluid shear without any tension. Cbfa1 expression was significantly greater in cells subjected to tensile forces than unstrained controls at all levels of strain tested (p< 0.05). Cbfa1 expression was further enhanced significantly by the addition of osteogenic factors (p< 0.05). Significantly greater mineralization (p< 0.05) occurred in the regions subject to tension with the greatest being in the region with an average strain of 1312 me.

Conclusions: Mechanical tensile forces especially in the range of up to 2173me promote differentiation of Mesenchymal Stem Cells into osteoblasts and encourage expression of the Cbfa1 gene. Tensile strain also promotes mineralization. Chemical factors in form of osteogenic media accelerate the differentiation of MSCs and encourages earlier production of osteoblast specific markers. Fluid shear appears to have a beneficial effect in stimulating differentiation into the osteoblast phenotype and, combined with tensile strain, may offer an even greater osteogenic stimulus.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1222 - 1227
1 Sep 2008
Jaiswal PK Aston WJS Grimer RJ Abudu A Carter S Blunn G Briggs TWR Cannon S

We treated 98 patients with peri-acetabular tumours by resection and reconstruction with a custom-made pelvic endoprosthesis. The overall survival of the patients was 67% at five years, 54% at ten years and 51% at 30 years. One or more complications occurred in 58.1% of patients (54), of which infection was the most common, affecting 30% (28 patients). The rate of local recurrence was 31% (29 patients) after a mean follow-up of 71 months (11 to 147). Dislocation occurred in 20% of patients (19). Before 1996 the rate was 40.5% (17 patients) but this was reduced to 3.9% (two patients) with the introduction of a larger femoral head. There were six cases of palsy of the femoral nerve with recovery in only two. Revision or excision arthroplasty was performed in 23.7% of patients (22), principally for uncontrolled infection or aseptic loosening. Higher rates of death, infection and revision occurred in men.

This method of treatment is still associated with high morbidity. Patients should be carefully selected and informed of this pre-operatively.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 304 - 304
1 Jul 2008
Sturridge S Hua J Ahir S Witt J Nielsen P Bigsby R Blunn G
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Introduction & Aims: A new femoral component for hip arthroplasty has been designed for a younger patient population. The design makes use of a higher femoral cut, which conserves bone stock, increasing options for future revision surgery. It uses the existing load bearing properties of the proximal femur, and therefore distributes load more evenly. The stem is longer than that of a resurfacing, so will be easier to insert at the correct orientation, minimising failure rates in inexperienced hands. The cross-sectional dimensions have been designed to produce torsional stability. The collar maximises the loading of the calcar, reducing stress resorption. The surface is hydroxyapatite coated and porous, which will produce a long-term biological fixation.

This project assessed the long-term stability of this design at different orientations, by measuring the change in surface strain distribution following its insertion.

Methods: Ten composite bones were coated in a Photoelastic material, positioned at a simplified single leg stance, and loaded at 2.3 KN. The surface strain was measured at one-centimetre intervals down the medial cortex. Then the prostheses were inserted into the bone at 135°, 145° and 125° to the femoral shaft, and the surface strains reread.

Results: The results were compared with an FEA model, and analysed statistically using the Wilcox signed rank test. The prosthesis inserted at 135° produced no significant difference in surface strain distribution compared with the intact bone.

Conclusions: This study suggests this stem design will be stable in the long term following insertion, and there were no areas of excessively high or low strain.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 380 - 380
1 Jul 2008
Fang S Ahir S Blunn G Goodship A
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We previously demonstrated that cartilaginous tissue was induced on a reamed acetabular articulation in an ovine hemiarthroplasty model with three different femoral head sizes. At maximum loading during stance phase, the acetabular peak stresses immediately after reaming could reach approximately 80 MPa under direct implant-bone contact with in-vitro measurements.

We aimed to establish finite element (FE) models of the ovine hip hemiarthroplasty which examine stress distribution on the reamed acetabula by three head sizes. We hypothesized that the stress distribution did not differ between different sizes when the joint is congruent and that the peak stresses in the acetabulum immediately after reaming occurred in the dorsal acetabulum.

Three two-dimensional FE models of ovine hip hemi-arthroplasty were built; each comprised a head component, 25, 28, and 32 mm in diameter, and an acetabular component. The acetabular geometry was acquired from an ovine acetabular histological section. The head was moved to partly intersect with the acetabulum representing the reaming procedure and a congruent contact was confirmed. Cortical bone and cancellous bone were modelled as linear elastic, with moduli of 20 and 1.2 GPa, respectively. Variable moduli were also assessed. The finest mesh for each model consisted of over 100,000 four-node quadrilateral elements. Loading conditions were chosen to represent peak hip joint force developed during the stance phase. Stress distribution in the acetabular area in contact with the head was plotted against the articulating arc length.

The results confirmed that the stress distribution between different prosthetic head sizes in a reamed hemiarthroplasty model did not change when the joint was congruent. The peak compressive stresses occurred in the dorsal acetabulum with the 32 mm model being the highest at approximately 69 MPa, the 28 mm model at 63 MPa, and the 25 mm model at 54 MPa. An increase in the cancellous modulus and a decrease in the cortical modulus increased the peak stresses in the dorsal acetabulum.

This presents an indicative study into the effect of prosthetic femoral head sizes on the stress distribution in the acetabulum. The idealized 2-D models showed reasonable agreement when compared quantitatively with the in vitro study.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 370 - 370
1 Jul 2008
Unnithan A Wells R Blunn G Goodship A
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Background: As the understanding of bone repair mechanics has advanced the integrity of the bone pin interface has emerged as a key factor in determining the success of external fracture fixation. The benefits of using pins coated with Hydroxyapatite (HA) are well documented however the thickness of the conventional plasma spray coating precludes its use for modification of the surface of fine features in implants. Consequently new electro-chemical techniques for pre-coating implants with a ‘biomimetic’ HA layer using simulated body fluids (SBF) have been pioneered. In this study we test the hypothesis that varying the technique for deposition of HA by electrolysis of SBF alters the morphology of the HA surface which will modify the level of osseointegration. Method: Three alternative methods of HA coating the Barerre, Redepenning and Kumar techniques were compared. Tantalum coated stainless steel pins were coated then used to stabilise a mid-diaphyseal osteotomy in three sheep using an orthofix fixator for a period of ten weeks. Insertion and extraction torques were measured to calculate the pin performance index (PPI). Sections of the bones were then examined using scanning electron microscopy to determine the percentage of bone in contact with the pin surface and the percentage of new bone formation. Results: The different coating protocols resulted in different HA crystal morphologies. The extraction torque exceeded the insertion torque for both the Barerre and Redepenning methods and their PPI exceeds that of plasma spray coatings. The Redepenning technique was shown to perform sig-nificantly better than both the Barerre (p=0,001) and Kumar (p=0,001) techniques with 49.4% of the pin surface in contact with bone. These results were mirrored on analysis of new bone formation with the Redepen-ning technique showing 70.2% of new bone formation compared to the Barerre (55.4%) and Kumar (53.8%) methods. Conclusion: These results indicate that the Redepenning technique is the most effective for creating a bio mimetic HA coating in terms of bonding to bone and promoting new bone formation. This technique holds significant advantages over the conventional plasma spray technique for example the coating thickness can be easily controlled and additional proteins such as bone morphogenic proteins and antibiotics can be incorporated. It may therefore represent a new era in the use of HA coating.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 396 - 396
1 Jul 2008
Jaiswal PK Gupta A Al-Hakim W Pollock R Blunn G Cannon SR Briggs TWR
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Aims: The main purpose of this study was to evaluate hemiplevis replacements in patients with periacetabular tumours in terms of the functional results and implant survivorship of the prosthesis. The second aim was to evaluate the complications and how they might be prevented in the future.

Methods: Case notes, hospital databases and radiographs were reviewed in 51 patients treated in a 16 year period with a custom made hemipelvis replacement (Stanmore Implants Worldwide). There were 13 deaths and 4 were lost to follow up. Of the remaining 34 patients there were 18 males and 16 females with a mean age of 48.6 (range 14 – 71).

Results: At a mean follow-up of 78 months (range 7 – 204), 70% of patients were still alive and the most common diagnosis was chondrosarcoma (17 cases). There were 2 cases of prosthesis failure and 22 of the 34 patients had one or more complications (12 cases of infection (8 deep and 4 superficial), 4 nerve palsies, 2 dislocations and 7 others). 13 patients had to have a second operation. The mean MSTS score was 63.8% and the TESS score was 59.8%

Conclusion: Infection was the most common complication and was the most significant reason for reoperation. This method of reconstruction is associated with a high morbidity rate and should be performed only at specialist centres, but the functional and oncological outcomes are satisfactory.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 230 - 230
1 Jul 2008
Nguyen C Singh D Harrison M Blunn G Dudkiewicz I
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Introduction: Many mini compression screws are now available for fixation in procedures such as metatarsal osteotomies or arthrodeses of the foot.

The aim of the current study is to compare the compression forces achieved by mini compression screws on cortical and cancellous bone models.

Material and Methods: The screws that were tested are listed in the table below. The compression forces were tested by inserting a pressures load measurement cell between longitudinally-split sheep tibia as a cortical bone model and longitudinally split retrieved femoral heads as a cancellous bone model.

Results: The Headed AO 3.5 mm cortical screw gave the best compression force and the Bold was the weakest, both in cortical and cancellous bone. The relative compression forces of the other tested screws were different between cortical and cancellous bone. Compression with the headless screws was lost as soon as the screw penetrated through the cortex in the cortrical bone model.

Conclusions: The indications for using headless self-tapping screws should be reserved for fixation of cancellous bone or of metatarsal or Akin osteotomies where compression is not required for union. When compression is important, such as in MPJ, tarso-metatarsal or talonavicular arthrodeses, Headed AO 3.5 mm or 2.7 mm cortical or 4 mm cancellous screws, which give better compression, should be used.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 363 - 363
1 Jul 2008
Korda M Blunn G Little N Hua J
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Introduction: The current practice of impaction allograft to fill large defects in revision total hip replacements is sometimes useful but clinical results are inconsistent. Other studies have shown that addition of mesenchymal stem cells (MSC) in blocks of hydroxyapatite (HA) scaffold can enhance new bone formation in a critical sized defect. However, no study has been conducted on combined MSCs with morselised allograft and HA granules. It is hypothesized that impaction of allograft or HA granules seeded with MSCs or osteoprogenitors will enhance new bone formation compared with the groups without MSCs.

Materials and Methods: Six sheep were used for the study. Each sheep received 8 scaffolds which were embedded in both paraspinal muscles. Groups were: 1) 3.5g allograft, 2) 3.5g allograft with MSCs, 3) 3.5g allograft with osteoblasts; 4) 3.5g of 50:50 allograft/ HA, 5) 3.5g of 50:50 allograft/HA with MSCs, 6) 3.5g of 50:50 allograft/HA with osteoblasts; 7) a block of HA, 8) a block of HA with MSCs. The experimental scaffolds were seeded with either 10x106 MSCs/ml or 10x106 MSC-derived osteoprogenitors/ml, in 3ml autologous plasma. Grafts were impacted twenty times at 3KN. At eight weeks, samples were sectioned for histology analysis. Areas of new bone formation were measured as percentage to total available spaces. ANOVA was used for statistical analysis.

Results: Addition of MSCs increased new bone formation in allograft (4.98%), allograft/HA (5.15%) and HA block (7.09%) compared with their controls at 2.24%, 1.96% and 1.96% respectively. Statistical study showed significant increase in 50:50 allograft/HA with MSCs compared with 50:50 allograft/HA only (p=0.046) and 50:50 allograft/HA with osteoprogenitors (p=0.028). No difference was found in allograft groups. For the HA block groups, addition of MSCs showed a significant new bone increase compared to the control (p=0.028).

Conclusion: Addition of MSCs to the allograft and HA granules will enhance new bone formation after impaction which can be used for revision total hip replacements, especially when allograft and HA is mixed. However, addition of osteoprogenitors has not achieved the similar results. This study encourages a further clinical investigation of impaction tissue-engineered graft to repair bone defects in revision total joint replacements.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 374 - 374
1 Jul 2008
Gordon D Pendegrass C Blunn G
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Introduction: Intraosseous Transcutaneous Amputation Prostheses (ITAP) could overcome the problems associated with conventional stump-socket prostheses for amputees (pressure sores, pain, infections and unnatural gait), by attaching the external prosthesis directly to the skeleton via a skin penetrating abutment. Despite this, the skin breach introduces a potential route for infection. For success, a biological seal at the skin-ITAP interface is essential.

The protein Laminin-5 (L-5) is a ‘biological glue’, which is integral to epitheial cell adhesion. Covalently bonding L-5 to the ITAP titanium alloy (Ti6Al4V), may enhance the strength of the skin-ITAP interface.

Silanisation, a chemical technique that covalently bonds proteins to metals, could be used to bond L-5 to Ti6Al4V. We have assessed the characteristics L-5 silanised Ti6Al4V as a potential substrate for ITAP.

Method: To determine the maximum quantity of L-5 that could be silanised to Ti6Al4V, and its relative stability when soaked in foetal calf serum (FCS) over time; polished Ti6Al4V discs were silanised by immersing in aminopropyltriethoxysilane followed by glutaraldehyde. Radiolabelled rat laminin-5-I125 was then added. Discs were immersed in FCS for 4 days (37 C) and analysed at 24 hour intervals in a liquid scintillation counter. Un-silanised discs were used as controls.

Results: L-5 was successfully covalently bound to Ti6Al4V. 10ng, 100ng, 250ng and 500ng droplets yielded significantly more silanised L-5 (p< 0.05), but no difference was observed between 750ng and 1000ng. Percentage L-5 covalently bound ranged from 33% and 65%.

A small decrease in bound L-5 occurred after 24 hours of FCS soaking (p< 0.05), but subsequent to this no significant reduction was observed for 4 days (p< 0.05). Controls showed a significantly larger reduction after 24 hours (p< 0.05).

Conclusion: Covalently bonding L-5 to Ti6Al4V by silanisation can be achieved with predictable results. Large enough quantities can be immobilised to influ-ence cellular function. L-5 silanised to Ti6Al4V remains stable in vitro over time and is not removed. Following the study of cellular interactions with silanised L-5, a stable skin seal may be achieved at the transcutaneous portion of the ITAP.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 396 - 396
1 Jul 2008
Jaiswal P Gupta A Strokes O Pollock R Cannon S Briggs T Blunn G
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Aim: To study the remodelling of cortical bone around the passive growing component of an expandable endoprosthesis.

Introduction: When inserting the passive component of an expandable prosthesis a polyethylene sleeve is commonly used. The sleeve migrates towards the lateral cortex and causes a cortical reaction and hence the use of the sleeve has been discarded recently. This study quantifies the amount of cortical reaction and degree of cortical drift in patients that had sleeves and those that did not.

Material And Methods: We reviewed X-rays and case notes of all patients that had an expandable endoprosthesis in a 20 year period. The thickness of medial and lateral cortices of the tibial diaphysis was measured at 6 months and on the last follow up radiograph. The distance from the edge of the sleeve (or prosthesis) from the cortical edge was also compared. Retrieved components also had their histology reviewed.

Results: The sleeve shifted laterally on average by 2mm (range 0.5 – 3mm) and touched the cortex. This was associated with an increase in lateral cortical thickness by 2.27mm (range 1 – 3mm). When the sleeve was used the prosthesis was inserted in the mid-line. When the sleeve was not used the tibial component tended to be inserted in valgus.

Conclusions: The presence of a sleeve is associated with a cortical reaction and the sleeve tends to migrate laterally. The clinical implications of this and the evolution of the design will be discussed in the meeting.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 395 - 395
1 Jul 2008
Stokes O Al-Hakim W Park D Unwin P Blunn G Pollock R Skinner J Cannon S Briggs T
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Introduction: Since 1975, 6 types of extendable endo-prostheses have been developed at Biomedical Engineering, UCL, and Stanmore Implants Worldwide in conjunction with the surgeons at this centre.

Aims: To establish whether developments in design have had the desired effect of improving both implant survivorship and functional outcome.

Methods: This was a retrospective study using case notes, hospital databases and a radiological review, combined with contemporary functional outcome assessments (MSTS, TESS, SF36).

Results: 161 consecutive prostheses in 138 paediatric patients, between the years of 1983 – 2005, were implanted for primary bone tumours. Mean age was 10.3 (3 – 18), 81 were males and 57 females. There were 136 primary procedures and 25 revisions.

6 prostheses that used ball bearings to achieve length (designed in 1981) were implanted, 3 (50 %) were revised due to mechanical failure.

19 prostheses that utilised external C-washes (1998) to achieve length were implanted, 6 (32 %) were revised, half of these for mechanical failure.

Of the 98 minimally invasive prostheses (1992) that utilized an Allan key and screw-jack mechanism to lengthen, 14 (14 %) were revised, half of these for infection.

17 non-invasive extendable endoprostheses (2001) that are lengthened by electromagnetic coupling have been implanted so far. There has only been 1 (6 %) revision. This was due to full extension being reached.

Conclusions: Design improvements in growing endoprostheses since 1983 have led to improved survivorship. Initially this led to a reduction in mechanical failure and latterly to a reduction in infection, as indications for revision.

Key Words: Bone tumour, children, endoprosthesis, survivorship.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 14 - 14
1 Mar 2008
Rust P Kalsi P Cannon S Briggs T Blunn G
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Bone grafts are frequently used to augment bone healing. Autologous bone graft is the gold standard for osteogenesis but is limited by availability and donor site morbidity. The processing required to lower the immunogenicity of allograft also reduces the osteogeneic properties. Bone marrow contains mesenchymal stem cells (MSCs) which differentiate into osteoblasts, forming bone. Our study examined the use of bone marrow to enhance the osteogenic properties of allograft.

Bioactive proteins within allogenic bone graft stimulate marrow-derived MSCs to differentiate into osteoblasts, thereby increasing the osteogenic nature of the graft.

After informed consent, bone marrow aspirates were taken from five patients during orthopaedic operations. Freeze-dried ethylene oxide treated allograft, from a number of donors, was obtained from the bone bank. MSCs isolated from each marrow aspirate were grown on eight samples of test allograft. Further allograft was heated to 70°C to denature the osteogenic proteins and MSCs from each aspirate were grown on 8 samples, as a negative control. Osteoblastic differentiation of MSCs cultured on the types of allograft was compared.

Scanning electron microscopy confirmed that MSCs covered the allograft after 14 days. Transmission electron microscopy showed that cells on the test allograft were characteristic of osteoblasts and produced collagen extracellular matrix. The levels of osteoblastic proteins, ALP, osteopontin and Type I pro-collagen, produced by cells on test allograft were significantly greater compared with heat-treated control (P< 0.005), after days 7 and 14.

Our study showed that marrow-isolated MSCs could be successfully cultured on allograft. As the levels of osteoblastic proteins increased significantly when MSCs were grown on allograft, osteogenic proteins within allograft caused MSCs to change into osteoblasts. This confirms that autologous marrow MSCs could be grown on allograft to increase its osteogenic prior to grafting, resulting in increased rate of bony healing.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 175 - 175
1 Mar 2008
Mannan K Amin A Blunn G Briggs T Cannon S Unwin P
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Endoprosthetic reconstruction as a form of limb salvage in the management of malignant disease is common. We present our experience with custom-made distal femoral replacement as a form of limb salvage in the absence of malignancy.

49 cases of distal femoral replacement were identified using the unit database. There were 18 males and 31 females, with a mean age at operation of 62.3 years (range 26–86). There were 29 cases of failed total knee replacements, 8 cases of fracture associated with bone loss, non-union or deformity, 7 periprosthetic fractures, 3 aneurysmal bone cysts, and one case each of avascular necrosis and Gorham’s disease. Clinical and radiographic review of all available patients, including a functional assessment with the Musculoskeletal Tumour Society (MSTS) Score and Toronto Extremity Salvage (TES) score was undertaken.

The average follow-up was 5.4 years (range 1 to 29 years). Three types of endoprosthesis were used, rotating hinge, fixed hinge and arthrodesis prosthesis. One patient required amputation at 2 months following post-operative wound infection with methicillin-resistant staphylococcus aureus and subsequent inability to provide adequate soft tissue coverage. There was one revision at 16 months for deep prosthetic infection. 21 patients were available for functional follow-up. The mean MSTS score was 63.7 (range 16.0–86.7) and the mean TES score was 59.4 (range 9.4–87.5).

Custom-made distal femoral replacements have an established role in limb-salvage surgery for malignant disease. This series demonstrates the reconstructive capability of custom prostheses in non-malignant disease, where deformity causes functional embarrassment or when massive bone loss would normally lead to amputation.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 183 - 183
1 Mar 2008
Sanghrajka A Amin A Briggs T Cannon S Blunn G Unwin P
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The purpose of this study was to determine whether the low rate of mechanical loosening of the SMILES rotating hinge distal femoral endoprosthesis relates to the hydroxyapatite (HA)-coated, grooved collar of the femoral component.

A database was used to identify two groups of cases of primary distal femoral replacement with a custom-designed and manufactured SMILES endoprosthesis at our unit; those with the collared femoral component (“collar group”), and those without a collar (“non-collargroup”). From these two groups, patients were pair-matched for age and length of bone resection. A retrospective review of serial biplanar pairs of radiographs of each patient, assessing radiolucent lines and extracortical bone pedicle.

11 matched pairs were identified, (14 females, 8 males), with a mean age of 36 years, (range 16–66). The pathology was primary bone tumour in 20 cases, (17 malignant, 3 benign), and metastatic disease in 2 cases. Mean length of follow-up was 85 months, (range 27–122). Radiolucent line score (RLS) progression over time was significantly lower in the collar group, (0.01 vs 0.73, p=0.001) (fig. 1 & 2), as was the mean final RLS, (2.72 vs 7.81, p=0.02). Mean RLS per radiographic quadrant was 0.56 in cases in which a bony pedicle was ingrown onto the prosthesis, (exclusively in the collared-group), 2.41 in cases in which the pedicle was not ingrown, (most prevalent in the non-collared group), and 1.02 in those cases without any pedicle formation, (ANOVA analysis, p=0.0002).

This study demonstrates that the HA-coated, grooved collar significantly reduces the progression of radiolucent lines, and consequently the overall RLS, explaining the reduced rate of mechanical loosening of the collared endoprosthesis. A bony pedicle that does not incorporate onto the prosthesis surface may be associated with an increase in radiographic loosening.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 27 - 27
1 Mar 2008
Baghla D Angel J Siddique M McPherson A Johal P Gedroyc W Blunn G
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Interventional MRI provides a novel non-invasive method of in-vivo weight-bearing analysis of the talo-calcaneal joint. Six healthy males (mean 28.8 years) underwent static right foot weight bearing MRI imaging at 0o, 15o inversion, and eversion. Using known radiological markers the motion of the talus and calcaneum were analysed.

The calcaneum externally rotates, plantar-flexes and angulates into varus. The talus shows greater plantarflexion with similar varus angulation, with variable axial rotation. Relative talo-calcaneal motion thus involves, 6o relative talar internal rotation, 3.2o flexion and no motion in the frontal plane. Concurrently the talus moves laterally on the calcaneum, by 6.5mm, with variable translations in other planes.

The calcaneum plantar-flexes, undergoes valgus angulation, and shows variable rotation in the axial plane. The talus plantar-flexes less, externally rotates, and shifts into varus. Relative motion in the axial and saggital plane reverses rotations seen during inversion. The 8o of relative valgus talo-calcaneal angulation is achieved through considerable varus angulation of the talus, in a direction opposite to the input motion. This phenomenon has not been previously reported. From coronal MRI data, comparative talo-calcaneal motion in inversion is prevented by high bony congruity, whereas during eversion, the taut posterior tibio-talar ligament appears to prevent talar valgus angulation.

We have demonstrated that Interventional MRI scanning is a valuable tool in analysing the weight-bearing motion of the talo-calcaneal joint, whilst approaching the diagnostic accuracy of stereophotogammetry. We have also demonstrated consistent unexpected talar motion in the frontal plane. Talo-calcaneal motion is highly complex involving simultaneous rotation and translation, and hence calculations of instantaneous axes of rotation cannot effectively describe talo-calca-neal motion. We would suggest that relating individual and relative motion of the talus / calcaneum better describes subtalar kinematics.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 176 - 176
1 Mar 2008
Meswania J Taylor S Blunn G
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For the treatment of malignant bone tumours in immature patients, extending prostheses are used to maintain growth in the affected limb. This new prosthesis allows the implant to be lengthened by using electromagnetic coupling that is simple and easy to use.

Because of bone tumour, fourteen patients between the age of 8 and 15 years underwent bone replacement treatment and a further two patients, both male 18 and 61 years, received the same treatment to restore limb length discrepancy. These implants consisted of a telescoping shaft where the expansion is done by a power screw driven by a gearbox connected to a NdFeB magnet. This prosthesis is capable of being extended under an axial load of up to 1350N. This is in line with 76 distraction force measurements taken in 43 patients with growing prosthesis where extension was achieved by invasive procedure and where a force of up to 1513N for an extension of 6mm was recorded. Once implanted, the non-invasive prosthesis is extended by placing the limb through an external drive unit. As the drive unit is turned on, it produces a rotating magnetic field capturing the implant magnet causing it to rotate in synchronisation. At full speed, the implant grows at a rate of 0.23mm per minute.

Of the sixteen patients, seven have been extended with one to its full capacity of 63mm. During extension, the patients have no sensations of vibration, heat, stretching or any other kind although the faint vibrations could be heard by placing a stethoscope on bony protrusions such as greater trochanter. At each sitting, the patients were extended by approximately 4mm during normal outpatient clinics and were able to walk as before immediately after the treatment. Patients with knee joint were functionally assessed before and after the treatment and showed approximately 10° to 15° of reduction in knee flexion/extension.

This new extending mechanism in these prostheses has provided the patients a treatment, which reduces trauma infection and discomfort. The mechanism of extension is reliable and effective.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 154 - 154
1 Mar 2008
Amin A Sanghrajka A Blunn G Briggs T Unwin P Cannon S
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The purpose of this study was to evaluate the results of custom-made endoprosthetic reconstruction for both tumourous and non-tumourous conditions around the elbow joint.

28 consecutive cases of endoprosthetic elbow reconstruction, performed between 1989 and 2003, were identified using the unit database. There were 12 males and 16 females, with a mean age 48.9 years, (range 14–84). There were 16 cases of malignant tumour (10 primary, 6 secondary), 3 cases of benign tumour (one each of giant cell tumour, osteoblastoma and pigmented villonodular synovitis) and 10 non-oncological cases, (5 cases of fracture, 3 failed total elbow replacements and 1 infected synostosis). A distal humeral prosthesis was used in 16 patients, distal humeral and proximal ulna in 10 patients, proximal ulna with a humeral component in one patient and proximal radial replacement in one patient. Clinical and radiographic review of all available patients, including a functional assessment with The Toronto Extremity Salvage score (TESS) was undertaken.

28 consecutive cases of endoprosthetic elbow reconstruction, performed between 1989 and 2003, were identified using the unit database. There were 12 males and 16 females, with a mean age 48.9 years, (range 14–84). There were 16 cases of malignant tumour (10 primary, 6 secondary), 3 cases of benign tumour (one each of giant cell tumour, osteoblastoma and pigmented villonodular synovitis) and 10 non-oncological cases, (5 cases of fracture, 3 failed total elbow replacements and 1 infected synostosis). A distal humeral prosthesis was used in 16 patients, distal humeral and proximal ulna in 10 patients, proximal ulna with a humeral component in one patient and proximal radial replacement in one patient. Clinical and radiographic review of all available patients, including a functional assessment with The Toronto Extremity Salvage score (TESS) was undertaken.

Endoprosthetic reconstruction around the elbow joint is effective in a wide range of pathologies, allowing in most cases a reasonable level of function, even following two-stage revision for infection.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 2 | Pages 246 - 253
1 Feb 2008
Coathup M Smith N Kingsley C Buckland T Dattani R Ascroft GP Blunn G

An experimental sheep model was used for impaction allografting of 12 hemiarthroplasty femoral components placed into two equal-sized groups. In group 1, a 50:50 mixture of ApaPore hydroxyapatite bone-graft substitute and allograft was used. In group 2, ApaPore and allograft were mixed in a 90:10 ratio. Both groups were killed at six months. Ground reaction force results demonstrated no significant differences (p > 0.05) between the two groups at 8, 16 and 24 weeks post-operatively, and all animals remained active. The mean bone turnover rates were significantly greater in group 1, at 0.00206 mm/day, compared to group 2 at 0.0013 mm/day (p < 0.05). The results for the area of new bone formation demonstrated no significant differences (p > 0.05) between the two groups. No significant differences were found between the two groups in thickness of the cement mantle (p > 0.05) and percentage ApaPore-bone contact (p > 0.05).

The results of this animal study demonstrated that a mixture of ApaPore allograft in a 90:10 ratio was comparable to using a 50:50 mixture.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 11 - 15
1 Jan 2008
Jaiswal PK Jagiello J David LA Blunn G Carrington RWJ Skinner JA Cannon SR Briggs TWR

We have managed 27 patients (16 women and 11 men) with a mean age of 68.4 years (50 to 84), with failed total hip replacement and severe proximal femoral bone loss by revision using a distal fix/proximal wrap prosthesis. The mean follow-up was for 55.3 months (25 to 126). The mean number of previous operations was 2.2 (1 to 4). The mean Oxford hip score decreased from 46.2 (38 to 60) to 28.5 (17 to 42) (paired t-test, p < 0.001) and the mean Harris Hip score increased from 30.4 (3 to 57.7) to 71.7 (44 to 99.7) (paired t-test, p < 0.001). There were two dislocations, and in three patients we failed to eradicate previous infection. None required revision of the femoral stem.

This technique allows instant distal fixation while promoting biological integration and restoration of bone stock. In the short term, the functional outcome is encouraging and the complication rates acceptable in this difficult group of patients.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 391 - 391
1 Oct 2006
Wells R Smith T Galm A Chatterjee B Pedersen S Goodship A Blunn G
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Introduction: External fixation is used widely in the management of fractures, despite a relatively high incidence of complication, arising from pin loosening and infection. Diamond like carbon (DLC) is a low surface energy coating that can be applied to external fixator pins and may reduce biofilm formation and infection resulting in a lower incidence of pin loosening. Hydroxyapatite (HA) is well established as a coating to enhance fixation of external fixator pins. This study tests the hypothesis that HA and DLC coatings on stainless steel (SS) external fixator pin shafts modify integration of the implant with soft/hard tissues.

Materials and Methods: An Orthofix external fixator was used to stabilise a tibial osteotomy with 6 self-drilling/tapping 6mm pins in 32 skeletally mature Friesland ewes. Animals were divided into four groups; SS, DLC, HA partially coated (threads only) and HA fully coated (threads and pin shaft). Pin insertion torque was measured using a torque wrench and extraction torque similarly obtained at 10 weeks when animals underwent euthanasia. Pin performance indices (PPI) were calculated as a ratio of extraction to insertion torque x100%. Pin site 2 was preserved for hard grade resin histology and subsequent pin tissue integration analysis. Pin site 3 was used for analysis of the soft tissue pin shaft interface using transmission electron microscopy. Pin site 5 was examined for the presence of biofilm formation using scanning electron microscopy. Pin site 6 was swabbed for microbiological analysis.

Results: SS and DLC pins achieved significantly higher insertion torques compared to HA partially coated pins (p=0.001, 0.002). Both groups of HA coated pins demonstrated a significantly higher, extraction torque and therefore PPI for all pin site positions compared to SS and DLC (p< 0.001– 0.025). The epithelium was found not to be in contact with the pin shaft in all cases. No significant differences were found between the different pin groups for epidermal down growth and dermal contact. Both groups of HA coated pins showed a significantly higher percentage of new bone in direct contact with the embedded threads compared to SS and DLC pins (p< 0.001, p=0.004). The proportion of soft tissue in contact and within the thread, of fully coated HA pins was significantly lower compared to stainless steel (p=0.003, p=0.017), DLC (p=0.004, p=0.002) and HA partially coated pins (p=0.006, p=0.02). Biofilms were evident on all pins except those coated with DLC. More bacteria were observed on the fully HA coated pins. DLC had significantly lower number of bacterial colonies in culture compared to SS (p=0.028) and fully coated HA pins (p=0.005).

Discussion: Coatings of DLC and HA do have a significant affect on hard/soft tissue reactions. However coatings do not have a significant effect on epidermal down growth or dermal attachment to the pin shaft surface. DLC coated pins had the cleanest surface with no bio-film present and significantly lower numbers of bacteria present. Fully HA coated pins despite evidence of bio-film formation, bacteria and high microbiological counts had significantly higher PPI. In addition fully coated HA pins demonstrated significantly reduced amounts of soft tissue at the pin bone interface. Therefore soft tissue reactions may affect bone integration.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 368 - 368
1 Oct 2006
Gouldson S Coathup M Blunn G Sood M
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Introduction: One of the most common complications following total joint surgery is aseptic loosening. Improving the bone-cement interlock may increase implant longevity. An ideally prepared bony surface is dry; clean; free from marrow, fat and debris; free from active bleeding; and free from micro-organisms. Lavage removes debris, blood and fat from the interstices of the bone surface so as to allow optimal penetration of the cement. The hypothesis that we investigated in this study was that lavage with a detergent solution obtains a greater depth of cement penetration into bone compared with lavage using 0.9% saline, hydrogen peroxide or an alcohol solution.

Methods: The cancellous bone of ovine femoral condyles were cut into 10×10×13mm blocks. Lavage solutions were delivered via a pulsatile system and directed towards one side of the bone block. All blocks were swabbed dry. A high viscosity cement was manually mixed and applied to the sandblasted surface of titanium alloy plate (10×10mm, weight 0.9g ±0.01g). The titanium plate and cement were placed on the irrigated bone block, and a known weight applied to achieve pressurisation. Time, temperature and method were controlled. The prosthesis-cement-bone composite was sectioned perpendicularly, and image analysis used to quantify penetration depths. 10 readings were recorded per block with 6 blocks per lavage group.

Results: Cancellous bone porosity averaged 75.2% (±4.0) . The mean penetration depth in the saline group averaged 3.39mm (± 0.77); 3.04mm (± 0.59) using a 2% alcohol solution; 3.33mm (±0.79) using a 3% hydrogen peroxide solution; and 5.41mm (± 1.30) when using the detergent lavage. There was no significant difference in cement penetration depth between hydrogen peroxide and saline irrigation (p> 0.05), nor with hydrogen peroxide and alcohol irrigation (p> 0.05). Irrigation with saline however, afforded statistically superior cement penetration than that of alcohol lavage (p < 0.012). Irrigation with detergent solution demonstrated significantly greater depth of penetration than all three other lavage groups (saline p< 0.05; alcohol p< 0.05; hydrogen peroxide p< 0.05).

Discussion: Detergents can physically remove particulate matter and emulsify and remove fats, thereby acting to maximise porosity of the cancellous bone network and optimise space for occupation by intruding cement. This study has proven the ability of a detergent solution to provide a clean, debris free cancellous network, which consequently provides a significantly greater depth of cement penetration than other commonly used irrigating agents. It was noted that cement penetration into cancellous bone followed the line and depth of cleaning from lavage. In conclusion, the hypothesis can be accepted, and lavage with a detergent solution affords a statistically greater depth of cement penetration into bone than that of the universally used 0.9% saline lavage.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 390 - 390
1 Oct 2006
Heidari N Korda M Dattani R Hua J Blunn G
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Introduction: Periprosthetic bone loss, brought about by wear particle induced osteolysis, presents a major challenge and compromises outcome in revision Total Hip Replacement. Poor bone stock at revision hip replacement is the main indication for impaction allografting. There are well documented limitations in the use of bone graft. Autogenous bone graft is osseoinductive, though donor site morbidity and the limited amount available restrict its use. An alternative is allogenic bone graft from cadaveric femoral heads. The drawbacks of using allograft are a limited supply and the risk of disease transmission. An alternative may be the use of bone substitute materials. Usually these are used in conjunction with allograft and therefore a number of drawbacks still apply. This study investigates the use of impaction grafting without bone graft. In this study we tested Apopore, 60% porosity, 2–5 mm hydroxyappatite (HA) granules (ApaTech Ltd) in an animal impaction model with allograft as control. Hypothesis Impaction using porous granular HA induces a similar volume of new bone compared with impaction using allograft.

Methods and Materials: Cylindrical defects of 15mm diameter were created in the medial femoral condyles of 12 sheep (6 sheep in each group) and filled with 3.5 grams of either morselised ovine allograft, washed and defatted according to North London Tissue Bank protocols, or porous HA granules impacted with a specially designed impactor, 20 times with a force of 3 KN. This force was similar to that measured during impaction grafting in clinical cases. After 6 weeks the sheep were euthanized, samples embedded in resin and the amount of bone formation measured by histomorphometric analysis.

Results: Under the impaction forces used the HA graft was more impacted than allograft. In the impacted HA graft the average pore size was smaller than for impacted allograft. After 6 weeks more new bone formation was observed at the host implant interface than the middle of the implant in both groups. At the implant host interface there was 26.64% (± 2.13%) new bone formation in the allograft and 21.13% (± 4.51%) new bone formation in the HA implant. In the middle of the implants allograft produced 11.01% (± 2.07%) new bone whilst the HA produced 7.23% (± 4.05%) new bone. Two tailed t-test showed no significance in either region, p=0.28 at the interface and p=0.40 in the middle. Allograft underwent resorption, from 39.37% at time zero to 5.66% (± 2.04%) at 6 weeks, a total reduction of 85%, where as the volume of HA granules remained the same and was 49% at time zero and 48.59% (± 1.69%) at 6 weeks. Two tailed t-test showed a significant difference (p< 0.0001) between allograft and HA at 6 weeks.

Conclusions: This study shows that granular porous HA induced a similar level of bone formation as compared with allograft. Resorption of allograft in this model allowed greater ingrowth of fibrous tissue. This makes the structural scaffold much more porous, compromising stability of the construct. The HA was not resorbed after 6 weeks and hence may be more stable. HA also has the advantage of being readily available. This study demonstrates that a bone substitute material does not need to be mixed with allograft.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 369 - 369
1 Oct 2006
Blackburn J Coathup M Smith T Goodship A Blunn G
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Introduction: The main problem facing the longevity of total hip replacements (THR) is wear particle induced osteolysis, particularly around the acetabular component. The articulating surfaces produce wear particles that migrate in the fibrous tissue membrane along the acetabular implant-bone interface causing osteolysis and subsequent implant loosening. The hypothesis that we investigated was that uncemented acetabular interfaces are more effective than cemented implants at resisting progressive osteolysis through bone attachment and the formation of a biological seal.

Methods: THR surgery was performed in an ovine model. Implants remained in vivo for 1 year. Femoral heads were roughened in order to generate wear debris and aseptic loosening of the acetabular component. Sheep were randomly assigned to one of three experimental groups: cemented polyethylene, grit blasted or plasma sprayed porous acetabular components with a polyethylene insert. Ground Reaction Force (GRF) data was collected pre-op and at 12, 24, 36 and 52 weeks post op. Retrieved specimens were analysed radiographically, histologically and using Scanning Electron Microscopy (SEM). A mould was made of the polyethylene liner and head penetration rates quantified using a shadowgraph technique. Thin sections through the acetabuli were prepared and image analysis used to quantify fibrous tissue (FT) thickness at the bone-implant interface. Mann-Whitney U tests were used for comparative statistical analysis where p< 0.05 were classified as significant.

Results: GRF demonstrated functional hips. A gradual increase was seen until week 36 followed by a decrease until retrieval suggesting the onset of aseptic loosening. 42.86% of control, 60% of grit blasted and 50% of porous coated components were deemed radiographically loose. Mean linear penetration rates demonstrated significantly less penetration within the porous cups (p=0.003, control and p=0.036, grit blasted). SEM established that wear particles generated were < 1μm in size. Light microscopy of thin sections revealed the common mechanism of loosening involving a resorption wedge at the interface with progressive bone loss. In all cases, the FT layer was greatest at the rim of the cup and gradually decreased towards the apex. The grit blasted group had the thickest FT layer adjacent to the cup. Under polarised light, wear debris was seen packed within macrophages in all sections.

Discussion: GRF data demonstrated grit blasted cups to have least function. This was confirmed through histology as they had the thickest FT layer surrounding the acetabular shell suggesting increased aseptic loosening of its component due to wear particles being able to access the interface more easily. Data corroborates radiographic results. In conclusion, porous and control cups performed better than grit blasted cups. Acknowledgments: EPSRC.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 373 - 373
1 Oct 2006
Aderinto J Blunn G
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Introduction: Human bone marrow stromal stem cells(BMSSC’s) have the ability to differentiate into a variety of mesenchymal cell types including osteoblasts, fibroblasts, adipiocytes and myocytes. These stromal cells are involved in the process of bone formation during the healing of fractures. Collagen lyophilisate is a sterile extract of bovine demineralised bone matrix. This material contains proteins removed from bone that may control the differentiation of osteoblasts from BMSSC’s. These proteins are localised within collagen type 1. The aim of this study was to determine the effects of collagen lyophilisate on the osteogenic differentiation of bone marrow stromal stem cells cultured in vitro.

Methods: Bone marrow was aspirated from the iliac crest of a human donor who was undergoing an unrelated elective orthopadic surgical procedure. Stromal stem cells were isolated from marrow, cultured and then characterised using immunofluorescent antibodies to Stro −1, a stromal stem cell marker. 3x104 BMSSC’s were seeded into each of 3 culture wells and incubated with standard growth medium or standard medium with collagen lyophilisate diluted 1:50 or 1:100. Cells were cultured for a maximum duration of 30 days. At selected time intervals until day 30, osteogenic differentiation was assessed by determination of alkaline phosphatase, osteopontin, pro collagen carboxyterminal (type 1 collagen synthesis) and calcium in cultures using specific assays.

Results: Cells cultured in collagen lyophilisate displayed a polygonal morphology early in the culture period and later formed complex aggregates. Cells in control cultures maintained a fibroblstic morphology until confluence. On day 21 alkaline phosphatase activity was significantly higher in collagen lyophilisate containing cultures than control cultures. Osteopontin levels were not enhanced in the collagen lyophilisate containing cultures. Type 1 collagen synthesis was higher in the collagen lyophilisate 1:50 group than all other groups at day 14. No differences in type 1 collagen synthesis were detected between cultures at other time periods. Calcium was not detected in any of the control cultures for the duration of the culture period. In contrast, calcium was detected in collagen lyophilisate containing cultures on day 15.

Conclusion: Collagen lyophilisate resulted in changes in cellular morphology and arrangement. The ability of collagen lyophilisate to enhance alkaline phosphatase activity, increase collagen type 1 expression and stimulate the deposition of calcium in stromal stem cell cultures provides evidence that it has osteogenic properties.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 373 - 373
1 Oct 2006
Phipps K Saksena J Gie G Muirhead-Allwood S Goodship A Blunn G
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Introduction: Impaction allografting is a technique that is used at revision where the bone stock in the femur is poor. Femoral heads are ground to create morsellised bone, which is impacted down the femur prior to the cementing a new stem into the canal. The results of this technique are variable and there is a high incidence of stem migration. This variation in results may be due to the degree of bone loss or the techniques used to impact the graft. The aim of this study was to quantify the forces currently used in revision hip surgery with impaction allografting.

Methods: To enable these measurements the Exeter slap hammer (Stryker Howmedica) was altered to include a load washer. The load washer had a special cable welded to it so that sterilisation could still be conducted in an autoclave. During surgery the end of the load washer cable is passed to the operator, who is able to connect it to a laptop computer. A specially written Labview program is then used to store the data and determine the impaction forces. The load washer is mounted within the hammer at the point of impact between the sliding mass and the hammer, consequently it is reading the force transmitted to the hammer, not that transmitted to the graft chips. Calibration was performed in an in vitro experiment with a second load washer, which found that the force in the hammer is three times that in the impactor. The force is so much less because it is taken up in the hammer’s inertia.

Conclusions: The impaction forces have been measured during eight operations performed by three different surgeons. The study shows variability between surgeons, and variability between patients operated on by the same surgeon. These readings show that the forces travelling through the impactor range between three to eleven time body weight.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 393 - 394
1 Oct 2006
Hua J Baker M Muirhead-Allwood S Mohandas P Nothall T Blunn G
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Introduction: The Resurfacing Hip has been increasingly popular for younger patients. Femoral neck fractures are still the main complication. The problems associated with cement such as thermal necrosis, cement debris and lack of long-term biological fixation, combined with the general use of cementless fixation in young patients invite the question whether a cementless component can be used for resurfacing hip replacement. Given that the cement may reinforce the femoral head preventing collapse, an additional question regarding the effect of bone density in cemented and cementless fixation can be asked. The hypotheses of the study are that:

High bone density will increase the yield point and stiffness of the femoral head and therefore improve the implant fixation.

Cement fixation will increase the yield point and stiffness of the femoral head, especially for the lower density bone compared with cementless fixation.

Materials and Methods: Thirty-six femoral head specimens were obtained from consented patients receiving routine hip arthroplasty. The heads were stored frozen at −20oC until use. pQCT was used to analyse trabecular bone density within each head. Specimens were ranked according to bone density and were assigned to high and low bone density groups. Cemented and cementless fixations were then alternatively assigned to individual heads in each group. Thus the 4 groups included in the study were: High density cemented, high density cementless, low density cemented, and low density cementless. Implantation of Birmingham resurfacing hips was carried out according to recommended surgical procedures. For cementing groups, surgical simplex P bone cement was used. Each sample was potted in a cylindrical polyethylene block for testing. A compressive load up to 5 or 10 KN using a Hounsfield Universal Testing Machine were applied on each sample at a rate of 1 mm min-1. Load versus displacement graphs were plotted for all tests. Yield point and stiffness were measured for each sample.

Results:

For yield point, there is no significant difference between cemented or cementless resurfacing (4169 ± 1420 N vs. 3789 ± 1461 N; P = 0.434). However, the high density heads provide a significantly higher yield point than low density heads (4749 ± 1145 N vs. 3208 ± 1287 N; P = 0.01).

The addition of cement significantly contributes to femoral head stiffness compared to cementless resurfacing (5174 ± 1730 N/mm vs. 3678 ± 1630 N/mm; P = 0.012).

Discussion: Bone density plays an important role in resurfacing hip arthroplasty. Higher bone density will reduce the incidence of fractures comparing with lower density. Therefore, resurfacing THR for the older patients and those with sub-optimal bone density should be used with caution. Consequently, it is suggested that a bone density scan should be routinely applied for those patients who are considered for resurfacing hip replacement. There is no difference between the cemented and cementless fixation in reducing femoral head failure, though cement will increase the stiffness of the bone. The study suggests that cementless resurfacing hip could be an alternative design with its clinical advantages of long-term osseointegration if implant is coated with bio-active materials.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 364 - 364
1 Oct 2006
Pendegrass C Annand B Hoare C Unwin P Goodship A Blunn G
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Introduction: Normal limb use in amputees with made to measure external prostheses can be impaired by problems at the stump – socket interface. The development of an Intraosseous Transcutaneous Amputation Prosthesis (ITAP) would overcome the problems by protecting the soft tissues, whilst redistributing high stresses to bone. ITAP creates a breach in the skins protective barrier to infection, hence requires a sufficient soft tissue – implant seal to prevent implant failure. Deer antlers are natural analogues of ITAP, and successfully overcome the problems associated with skin penetrating implants such as infection, marsupilisation and avulsion. In this study, an ITAP device has been developed, with a successful soft tissue – implant interface, based on deer antler morphology. It is hypothesised that sub-epithelial dermal fibroblastic, but not epithelial layer adhesion, is directly responsible for the degree of downgrowth observed around ITAP.

Methods: Eleven pairs of deer antler were used to histologically evaluate the interface between the antler and pedicle, and the soft tissue seal around the antler-pedicle structure. The findings were used to develop a titanium alloy (Ti6Al4V) ITAP device in a goat model. Three to five transcutaneous pins were implanted into the medial aspect of the right tibia of skeletally mature female goats. Four implant designs were tested, Machine Finished Straight (MFS), Hydroxyapatite (HA) Coated MFS, Machine Finished Flanged (MFF) and HA Coated MFF. The 70μ thick HA coating was applied to the implant region abutting the sub-epithelium. The implants remained in situ for four weeks after which the histology of the resulting interfaces were analysed qualitatively and quantitatively for degrees of epithelial downgrowth (marsupilisation) and epithelial/sub-epithelial layer attachment to the implant surface.

Results: The histology of the deer antler showed there to be an extremely small area of epithelial attachment, with negligible downgrowth, arrested by soft tissue adhesion to the underlying pedicle surface. There was a significant increase in pore size and frequency in the pedicle structure (abutting the soft tissues), compared to the antler proper. The MFS ITAP implants were associated with significantly greater downgrowth and reduced epithelial and sub-epithelial layer attachment compared to all other implant designs. The HA coating, and porous flange structure significantly reduced downgrowth and increased sub-epithelial layer attachment. Regression correlation showed that there is a significant negative correlation between the extent of downgrowth and the degree of sub-epithelial dermal fibroblastic layer attachment observed around ITAP implants (All p values < 0.05).

Discussion: Deer antlers successfully overcome the potential problems for ITAP. By artificially recreating some of the aspects of the antler, including layering of porous and bioactive surfaces for tissue adhesion, we have successfully developed an ITAP implant that minimises downgrowth and actively encourages epithelial and sub-epithelial soft tissue adhesion.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 397 - 397
1 Oct 2006
Caruana J Mannan K Sanghrajka A Higgs D Blunn G Briggs T
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Introduction: Surgeons in the UK and Europe generally use a thinner cement mantle than their counterparts in the USA for the femoral component in total hip replacement (THR). The aim of this study was to compare the performance of different thicknesses of cement mantle using finite element analysis. The measures by which comparison might be made include cement cracking, subsidence, migration and stress shielding. In this study, we use a linear-elastic model of the implanted femur to give a prediction of the stresses in the cement mantle and in the femoral cortex. These measures give an indication of the relative rates of cement cracking and loss of bone stock due to stress shielding. To assess the reliability of our model in representing patients with different bone densities, we use a range of cancellous bone stiffnesses.

Method: Two cadaveric femora from the same donor were sized, reamed and implanted with identical plastic replica femoral components following standard surgical technique for the Stanmore Hip system. One was prepared using UK rasps, over-reaming by ~2mm, the other using US rasps, over-reaming by ~5mm. Serial CT-scans were used to create three-dimensional geometric models of the implanted femora. Two finite element meshes were hand-built in MSC. Marc finite element software, incorporating cortical and cancellous bone, bone cement and prosthesis. Each model consisted of 10,000 eight-noded brick elements, with a fully bonded stem-cement interface. The thick and thin cement mantles had thicknesses of 2.5mm and 1.0mm respectively, in regions where thickness is affected by rasp size. Models were identical in the distal medullary canal. Cortical bone was modelled as transversely isotropic, with longitudinal and transverse moduli of 17.0 and 11.5 GPa. Bone cement was given a modulus of 2.7 GPa. Loading conditions were chosen to represent the heel-strike phase of gait. In order to assess the impact of variability in patient bone density, cancellous bone modulus was varied between 0.06 and 2.90 GPa.

Results: Equivalent stress was examined on the external surface of the cortex and the internal surface of the cement mantle. The lowest cortical bone stresses were proximal and the highest cement stresses around the distal tip of the prosthesis. In the proximal cortex, higher equivalent stresses were observed medially and laterally with a thick cement mantle. Distally, lower cement stresses were observed in the thick cement mantle. With the highest cancellous modulus, there was little difference between the two models. As this modulus was reduced, stress differences between the models became more apparent. For all cancellous bone moduli, peak distal cement stresses were lower and minimum proximal calcar stresses higher in the thick cement mantle.

Discussion: Proximal stress shielding was greatest in the calcar, in agreement with clinical findings. The thicker cement mantle led to less stress shielding in this region. Cement stresses, highest around the distal tip of the prosthesis, were larger in the thin cement mantle. This suggests a higher rate of both cracking and bone resorption in thin cement mantles. Although observed over a range of cancellous bone stiffness, this finding applies particularly to patients with low bone density.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 401 - 401
1 Oct 2006
Sanghrajka A Mannan K Caruana J Higgs D Blunn G Briggs T
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Introduction: Aseptic loosening remains the commonest causes of failure of total hip arthroplasty. Cement mantle defects are associated with aseptic loosening. This study aimed to determine a correlation between surgical approach and cement mantle defects in the Stanmore Hip. The Stanmore total hip replacement was chosen because it has greater than an eighty-five percent survivorship over 25 years and unlike other prostheses with comparable results such as the Charnley total hip, it remains essentially unchanged to date.

Method: This was a retrospective review of all Stanmore hips. AP and lateral radiographs were available for 62 patients operated via the posterior approach and 100 patients operated via the anterolateral approach. The mean cement thickness in all fourteen Gruen zones was estimated for each patient. Gruen zones IV and XI, representing the stem tip, were removed from data relating to mantle thickness. Mantles were graded as less than 2mm, 2–5mm, 5–10mm and more than 10mm. Alignment was also measured.

Results: Fifty-nine percent (32/54) of cement mantle defects are seen in Gruen zones VIII to XIV. The mean cement mantle thickness in A-L approach was 3.11mm compared to 4.23mm with the posterior approach. This corresponds with the frequency of cement mantle defects occurrence. No cement defects were seen in Gruen zones IV or XI. Using the anterolateral approach, defects were observed in 49 out of 1200 zones (4.08%) and using the posterior approach in 6 out of 744 zones (0.81%). With the anterolateral approach, 19 out of 100 cement mantles (19%) had defects, compared to only 3 out of 62 (4.84%) with the posterior approach. Defects were most commonly seen in zones I, V, VIII and XII, which corresponds to valgus and posterior orientation of the stem.

Discussion: The posterior approach does generate a more uniform cement mantle. Several studies suggest that a cement mantle smaller than 2mm or greater than 10mm can be detrimental to the survivorship of the arthroplasty. This study suggests that a deficient cement mantle is more likely using an anterolateral approach.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 409 - 409
1 Oct 2006
Caruana J Hon C Whittingham-Jones P Briggs T Blunn G
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Introduction A consensus exists regarding the optimal range of femoral cement mantle thickness in hip replacement. However, within this range surgical preferences differ, surgeons in Europe generally preferring thinner cement mantles whilst those in the US prefer a thicker mantle. For a given implant size, the rasps provided in the US for use with the Stanmore Hip are larger than those used in Europe, producing a thicker cement mantle. The integrity of the femoral cement is considered to be crucial to the long-term survival of cemented hip replacements. Previous studies have used cement cracking under fatigue loading as a comparative measure of implant survival. Damage accumulation levels between different implants are associated with clinical failure rates. The aim of this study was to compare the cracking behaviour of cement mantles of different thicknesses around Stanmore Hip replacements. We hypothesised that a thicker cement mantle would lead to reduced cement cracking.

Methods Ten synthetic femurs (Sawbones) were prepared following standard surgical practice for the Stan-more Hip. Five of these were rasped using the larger US rasp, and five using the European version. Stanmore Hip femoral components were then cemented into the femurs with Palacos-R cement and using a custom insertion rig to ensure good alignment and centralisation, confirmed by radiographs. The femurs were then cyclically loaded with an aggressive 4 kN stair-climbing load for 4 million cycles at 3 Hz. The femurs were sectioned at 5 mm intervals and dye penetrant used to highlight cement cracks. Image analysis software was used to measure cement thickness and crack lengths under light microscopy.

Results The minimum cement mantle thickness per section was found to average 0.8 mm and 2.0 mm for the thin and thick mantle groups respectively, measured around the proximal half of the implant. This was significantly different (p< 0.05). Cracks in the cement mantle were irregularly distributed along the length of the prostheses. We found no significant difference in either the total number or total length of cracks found in each group. These were investigated over the whole mantle and by Gruen Zone.

Discussion The geometric and mechanical properties of human femurs vary considerably, which might be expected to increase dramatically the scatter in any clinical trend relating cement thickness to cracking. Our study, using identical synthetic femurs and well-centralised prostheses to minimise experimental variability, found no difference in cracking. Given this experimental consistency, it is thought that there would be no clinically significant difference in cracking rates between different cement thicknesses within the normal range for the Stanmore Hip replacement. The Stanmore Hip is designed to minimise cement stress. A collar prevents subsidence-related hoop stresses, and smooth corners minimise stress concentration in the cement. It is likely that, for a sub-optimal implant design with higher stress risers, cement thickness might have a more noticeable effect on crack propagation.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 364 - 364
1 Oct 2006
Korda M Sharpe J Rust P Hua J Phipps K Di Silvio L Coathup M Goodship A Blunn G
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Introduction: Wear particle induced osteolysis is one of the main reasons for revision total hip replacements (THRs). Loss in bone stock as a result of aseptic loosening is responsible for inferior results in revision THRs. Results from impaction grafting to fill osteolytic defects are frequently inconsistent. Our hypothesis is that the combination of autologous mesenchymal stem cells (MSCs) and allograft will enhance bone regeneration. This study asks whether: MSCs with allograft scaffolds survive at a normal impaction force during revision THRs.

Method: MSCs were isolated from a sheep iliac crest aspirate, expanded in culture and seeded onto irradiated sheep allografts (n=9). Viability of MSCs was assayed with alamar blue with absorbance measured on day 4 (before impaction). The constructs were then impacted using forces 3, 6, and 9 kN extrapolated in surgery then assayed daily for 6 days. The control was 0 kN. Samples were resin embedded after 10 days for histology and pieces of graft were taken for scanning electron microscopy (SEM).

Results: The 0KN control shows an MSC growth curve with a lag period and log phase. Compared with the control, the 3 and 6 kN showed initial reduction in cell proliferation measured by alamar blue (^p=0.015, ^p=0.002) but recovered by day 8, while 9kN showed a significant reduction (^p=0.011) over the time (Figure 1).

For cell proliferation over time, 3 and 6 kN showed no differences, but 9 kN showed a significant difference between day 4 and day 8 (^p=0.031). SEM and histological analysis showed a network of cuboidal cells on the allograft surface.

Conclusions: The results showed that MSCs recovered from impaction of 3 and 6 kN after an initial reduction in metabolism and exceeded original cell seeding densities with no significant difference in proliferation. Viability of MSCs were not effected by impaction forces up to 6 kN. This study shows that stem cells mixed with allograft are a potential method for repairing bone defects in revision total hip replacements.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 370 - 371
1 Oct 2006
Biring G Meswania J Wylie C Muirhead-Allwood S Hua J Blunn G
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Introduction: To investigate the head/neck interface of total hip replacements and to see whether the use of small spigots (minispigots) results in enhanced wear and corrosion of tapers compared to standard spigots and the influence of the surface finish on this.

Methods: In the total hip replacement combinations the heads were made of cobalt-chrome (CoCr) and the stems of titanium alloy (Ti). Firstly wear and corrosion of minisigots were compared with standard spigots (Test 1) and secondly, these minispigots were compared with another minispigot with a smoother taper surface finish (Test 2). The samples were immersed in aerated Ringers solution (37°C) and loaded for 10 million cycles. The specimens surface parameters and profiles were measured before & after the test. Electrochemical static corrosion tests were carried out on the rough & smooth minispigots from Test 2 where the current was measured with constant potential under loaded and non-loaded conditions. A cyclical sinusoidal load of 1500-200 Newtons for 1000 cycles at ~1 Hz was used. Pitting tests measured the current while increasing and then decreasing the potential of non-loaded and loaded specimens. Two newly manufactured rough and smooth minispigots were subjected to the same electrochemical corrosion tests.

Results: In Test 1 the results demonstrated that pre-test the surfaces of the female tapers were similar for all heads. Post-testing the Ra values on the female tapers had become greater for the minispigots compared with standard spigots. An abrupt change was noted on the surface profile of the female taper where it was in contact with the male Ti taper, indicating the the CoCr head had corroded. The Ti male tapers were unchanged. Scanning electron microscopy showed that the coarser profile in the corroded region of the CoCr was similar to the profile on the Ti male taper. Pitting corrosion was evident in the grooves on the CoCr. In Test 2 the smooth spigots were not affected, but in the rough minispigots, Ra values had increased in the female tapers. Static corrosion tests showed evidence of fretting in the rough but not the smooth minispigots. When comparing new rough & smooth minispigots, static corrosion testing with clyclical loading showed that for minispigots with a rough finish the current fluctuated with each cycle. Pitting scans showed a greater hysteresis with the rough minispigot compared with the smooth minispigot indicating potentially greater corrosion in the former.

Conclusion: The cobalt-chrome/titanium alloy combinations where the surface finish on the male taper was coarse, corrosion was increased in minispigots compared with standard spigots. This was due to the smaller area of contact of the minispigot at the interface. This corrosion appears to be mediated through the mechanism of fretting corrosion. Surface finish was crucial and corrosion of the minispigot was reduced if the surface finish was smooth. Manufacturers should investigate the effect of surface finish on the corrosion of their tapers particularly where cobalt-chrome/titanium alloy combinations are used.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 392 - 392
1 Oct 2006
Kalia P Bhalla A Coathup M Miller J Goodship A Blunn G
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Introduction: The survival of massive endoprosthesis replacements is not as successful as conventional joint replacements. The main cause of failure of these implants is aseptic loosening. Bone in-growth onto the implant collar on the shaft of the prosthesis adjacent to the transaction site has been correlated with a decrease in radiolucent lines adjacent to the intramedullary stem and reduced implant loosening. We propose that bone contact and in-growth to the collar may be further enhanced with tissue engineering techniques. The hypothesis of this study was that autologous mesenchymal stem cells (MSCs) suspended within fibrin glue and sprayed onto hydroxyapatite (HA)-coated collars of massive prosthesis will augment bone growth and contact to the implant in an ovine model.

Materials and Methods: MSCs were isolated and expanded in vitro from the iliac crest of six adult sheep. Pre-implantation, 2 x 106 autologous MSCS were suspended in thrombin. During surgery, this mixture was combined with fibrinogen and sprayed onto the proximal and distal HA-coated collars of tibial midshaft prostheses using pressurized air. The implants were cemented into the right hind limb of twelve sheep, six of which received MSCs. Radiographs were taken at 2, 4 and 6 months and bone area within defined regions quantified using image analysis software. After six months, specimens were retrieved and processed for undecalcified histology. Transverse thin sections were prepared through the centre of each collar. Image analysis was used to quantify bone area and contact. Mann Whitney U tests were used for comparative statistical analysis, where p< 0.05 was classified as significant.

Results: Anterior-posterior (AP) radiographs taken at 2, 4, and 6 months showed that animals treated with MSCs produced more bone adjacent to the shaft of the implant. Analysis of bone area on both AP and medio-lateral (ML) radiographs taken after sacrifice showed that stem cell-treated implants encouraged significantly more total bone around the implants at 6 months than the control group (171.94 ± 29.04 mm2, and 87.51 ± 9.81 mm2 bone area, respectively, p = 0.016). Analysis of histological sections shows a significant increase in bone area around midshafts treated with MSCs, compared to the implant controls (53.99 ± 10.64 mm2, and 21.07 ± 7.34 mm2, respectively; p = 0.020). The average surface area contact between the midshaft and bone was almost doubled in the MSC-implant group (19.83 ± 8.73 % contact) than in the control group (8.667 ± 8.667 %, p = 0.196). In the MSC group bone was seen deep within the grooves of the HA coated collar whilst a fibrous soft tissue layer separated the newly formed bone in the control group.

Conclusion: Bone contact and in-growth to massive endoprostheses was significantly improved by spraying the implant with autologous MSCs suspended in fibrin glue. Enhanced fixation using stem cells may help prevent aseptic loosening in these massive implants.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 396 - 396
1 Oct 2006
Ferris B Ahir S Blunn G
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Introduction: Fragility of the bone is widely regarded as a cause of Colles’ Fracture particularly in middle aged or elderly women[1]. However not every fall results in fracture of the wrist. The normal volar angle of the distal radius is said to be about 10 degrees although in one study the mean volar angulation was found to be 12 degrees with a range from 4 to 23 degrees[2]. We hypothesised that the volar angle of the distal radius or the position of the wrist at impact could affect where the peak stresses occurred during a fall onto the outstretched arm. We investigated the effect of these two variables on the location and magnitude of the peak stresses using finite element analysis.

Materials and Method: A finite element model of the distal radius was constructed in MARC (MSC software, USA). The model was developed from CT data of the right wrist of a 46 year old male. The data was examined by edge detection software (Materialise, Belgium). The inner and outer boundaries of the cortex were imported as curves into MARC. A surface mesh of the distal radius was constructed, from which a 3D solid mesh of the distal radius was generated automatically. The volar angle was modified to represent between 5 to 25 degrees in 5 degree increments. The wrist position was also changed for each volar angle. This varied in 5 degree increments from 0 to 35 degrees, and then at 45, 75 and 90 degrees. Material properties assigned to cortical and cancellous bone were 20GPa and 6GPa respectively with a Poisson’s Ratio of 0.3. The model consisted of 17660 8 noded hexahedral elements and was fully fixed at the cut end of the proximal radius. For each volar angle a load of 500N and 400N was applied perpendicularly to the articular surface across the scaphoid and lunate fossa respectively. The magnitude and location of peak stresses in the proximal and distal radius were recorded.

Results: Results show that the location and magnitude of peak stresses vary as a result of wrist position. Distally the stress rises with increasing dorsiflexion and at 35 degrees exceeds the load to failure. The volar angle does not influence the stresses unless it is 20 degrees or more. Proximally the volar angle had no effect, but if the wrist is in more than 75 degrees of dorsiflexion then the peak stresses exceeded the load to failure.

Conclusion: Results show that a fall onto the outstretched arm will produce differential stresses in the radius depending on the position of the wrist at impact. The volar angle affected the stresses in the distal radius at greater than 20 degrees but proximally it did not. Proximally stresses above 130MPa (when the wrist is in more than 75 degrees of dorsiflexion) will subject the wrist to fracture[3]. Distally (when the wrist is in more than 35 degrees of dorsiflexion) with high volar angles (greater than 20 degrees) is likely to produce the conditions for a fracture (cancellous bone has been reported to fail as a result of fracture at 50 MPa [4] and for osteoporotic bone at 0.44MPa [4].


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 373 - 373
1 Oct 2006
Phipps K Pegrum J Smith N Blunn G
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Introduction: ApaPore is a synthetic bone graft extender, made from Hydroxyapatite. It is designed to be used as a 50:50 combination by volume with morcelised bone graft. A typical use for such a product may be in impaction allografting during revision hip surgery. The aim of this study was to compare the mechanical stability of stems inserted using impaction allografting where the graft was composed of a 50:50 mixture of ApaPore and allograft with only allograft.

Methods: Twelve large left sawbones were used in this study, the femoral head was cut off each one and the equivalent cancellous bone was cored out to resemble a femur at revision. Impaction allograft was performed on six of the sawbones, with rinsed human morsellised graft. This procedure was repeated on the remaining six sawbones, with graft produced as a 50:50 mixture by volume of rinsed allograft and blood soaked Apapore. The mechanical test was performed in the red rocket, a six station hydraulic loading machine. The sawbones were mounted in the anatomical position of 7 degrees valgus and 9 degrees posteriorly and the test was run in batches of three. Sinusoidal loading at 2Hz was applied under the following loads: 600N, 1kN, 1.4kN, 1.8kN and 2.2kN, each loading step lasting for 5000 cycles. Migration of the stem during loading was measured using LVDT. Vertical displacement of the prosthesis head was measured using digital height callipers at the beginning and end of each loading step. X-Rays were taken before and after mechanical testing.

Results: There is a significant difference between the groups in the overall displacement of the prosthesis head, measured with the digital height calipers, (Mann-Whitney U Test p=0.01). Total average head movement allograft group: 3.5mm and ApaPore group: 1.8mm. The total average subsidence measured with the LVDT’s was 0.295 mm in the allograft group and 0.119mm in the ApaPore/Allograft group. A sideways displacement of the prosthesis head was observed on the x-rays, which is a direct relationship of head rotation, measurements showed a significantly less rotation in the ApaPore/Allograft group (Mann-Whitney U Test p=0.002).

Conclusions: Rotation of the stem in all planes during loading resulted in a greater observed displacement of the prosthesis head than that measured by the LVDT’s. These results show that ApaPore, when used as a bone graft extender is able to reduce initial rotation and subsidence of the stem. Further research needs to be undertaken to investigate the long-term feasibility of using ApaPore.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 374 - 374
1 Oct 2006
Phipps K Goodship A Blunn G
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Introduction: Impaction allografting allows an initial stable function of revision hip replacements and a method of reconstituting the bone stock. A previous in-vivo ovine study has found that the density of impacted morsellised allograft reduces after six weeks but recovers by twelve weeks. This reduction in density during remodelling may also correspond with a reduced mechanical strength. A probable cause of the low density is osteoclastic bone resorption prior to vascular in growth and the formation of new bone by osteoblasts. BoneSave is a 4–6mm porous granules of hydroxyapatite and tricalcium phosphate, and is designed as be used as a 50:50 mix with morsellised allograft. Bonesave takes a long time to be resorbed and replaced with bone compared with allograft. We hypothesised that the inclusion of BoneSave could slow resorption down and hence maintain the mechanical strength of the graft during remodelling. This study investigated the mechanical strength of BoneSave mixed with allograft at six and twelve weeks after insertion into a defect, with pure allograft as a control.

Methods: Twelve yews were used in this study, half were terminated at six weeks the remainder at twelve. The test site was a 15mm diameter hole, approximately 10mm deep, in the medial femoral condyle. Both femurs were operated on consecutively, with allograft on one side and a BoneSave/allograft mix on the other. After euthanasia the distal femurs were removed and CT scans performed to evaluate density. Sixteen millimetre discs were cut from each femur, exposing the test site 4 mm from its proximal end. These graft site was then subjected to non-destructive compression tests in Zwick loading machine. Bone remodelling in the graft was determined using histology.

Results: Wilcoxon paired test were used to compare densities of the allograft group with the BoneSave group at 6 and 12 weeks, at both time points there was a significant difference between the groups (p< 0.05). There was no statistical difference in the density of the allograft groups between 6 and 12 weeks, or the Bonesave groups between 6 and 12 weeks using the Mann-Whitney U test (p> 0.05). There was no significant difference between the stiffness of the two groups at both time points using the Mann Whitney U test (p> 0.05).

Discussion and Conclusion: This result was unexpected in the allograft group because in a previous study looking at different sized allograft chips there was a significant difference between the density at 6 and 12 weeks. The most likely cause for this is that lower forces were used to impact the graft in this experiment compared with the graft size study. This would have resulted in lower density at time zero, so perhaps this lower density didn’t invoke such a large resorption response. Bone-Save is able to maintain mechanical strength during remodelling when used as a bone graft extender.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 397 - 397
1 Oct 2006
Gordon D Sun SNM Pendegrass C Blunn G
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Introduction: Transcutaneous Amputation Prosthesis (ITAP) is an alternative for transfemoral amputees to conventional stump-socket prostheses which have many problems. These include: poor fit, stump pressure sores, pain, infections and unnatural gait. ITAP aims to overcome these by being osseointegrated into the femoral medulla with a pin protruding through the skin to which the external prosthesis attaches. Thus, the forces normally encountered by the stump soft tissues are now transferred directly to the skeleton. However, the transcutaneous pin produces a route for infection from the external to internal environment. Therefore, a key feature to the success of the ITAP is to produce a biological seal at the transcutaneous interface. Epithelial cells have been shown to attach to dental transcutaneous titanium devices via hemidesmosomes (HD).2 Focal contacts (FC) are also important in cell adhesion and to the underlying substratum.3 We grew human keratinocytes on different titanium surfaces to assess their morphology, ability to proliferate and produce HD and FC. Hypothesis: Surface topography influences keratinocytes morphology and proliferative capacity and expression of HD and FC.

Materials and Methods: 4 titanium alloy (Ti6Al4V) surface topographies were used (10mm x 4mm discs): polished, machine finished, sandblasted and hydrofluoric acid etched (HF) and a control – plastic thermanox. Surface roughness profiling of titanium discs were measured (Mitutoyo Surftest SV-400). HaCaT keratinocytes were grown on disc surfaces in wells of culture medium at +37oC, 5% CO2 and analysed at 1, 2, 3 and 4 days. Cells were processed to visualise HD with fluorescence microscopy using antibodies to the 6-integrin and plec-tin. Anti-vinculin antibodies were used to visualise FC. Fluorescein isothiocyanate (FITC) secondary antibodies enabled counting of structures (all product: Sigma-Aldrich, UK). Alamar blue (Serotec, UK) measured cell proliferation and SEM (surface morphology, cell area) and TEM were also performed. Cells grown on polished, machined and thermanox discs supported a regular, confluent layer with many cytoplasmic processes and dividing cells. HF and sandblasted discs grew an irregularly layer with fewer cytoplasmic processes and fewer dividing cells (not quantified). Day 3 TEM revealed HD, FC and desmosomes; cells on polished and thermanox were more closely packed and in layers.

Conclusion: Keratinocytes are significantly influenced by titanium surface topography. Smooth polished titanium alloy may be the ideal surface for a transcutaneous pin in the ITAP. Further experiments into isolating favourable biological components needed to encourage keratinocytes to attach onto titanium should be carried out.

Results: No significant difference shown in cell proliferation between titanium discs but cells on thermanox grew significantly more (p< 0.05). FC and HD numbers increased on all surfaces (days 1–3); a negative correlation between surface roughness and HD and FC numbers observed (lower Ra values = more HD and FC expressed).


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 365 - 365
1 Oct 2006
Shoeb M Coathup M Witt J Walker P Blunn G
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Introduction: Conservative hip replacements are advantageous because resection of bone in the proximal femur is minimised. This study investigated a new design of conservative hip in the goat model where the femoral head was resected and two hydroxyapatite coated ‘pegs’ were introduced into the femoral neck. The hypothesis was that the ‘pegs’ would provide a direct method of transmitting forces within the femoral neck thus resulting in less adverse bone remodelling and reduced loosening. Bone stock is also preserved should subsequent revision be required.

Methods: Eight unilateral implants were inserted into the right femur of adult female goats for 1 year. Retrieved specimens were analysed radiographically and histologically. Image analysis was used to quantify bone attachment and total bone area adjacent to the implant. Tetracycline bone markers quantified bone turnover. Operated hips were compared with non-operated hips. The students t-test was used for comparative statistical analysis where p< 0.05 were classified as significant.

Results: Radiographic analysis demonstrated bone loss beneath the cup with increased bone density at the distal end of the pins (fig.1). Light microscopy revealed areas of new and mature bone adjacent to the implant. Osseointegration to the HA coating was observed. Bone markers established significantly decreased bone formation rates (p< 0.05) in bone adjacent to the implant in the operated versus control hips.

Image analysis results demonstrated an average bone attachment of 30.94% to the implant surface (fig 2). Greatest bone attachment occurred at the end of the pins (78.99%) contributing 22% of overall attachment to the implant. Least attachment occurred beneath the prosthetic cup (13.82%) and in the medial aspect adjacent to the central pin. Greater total bone area was measured in control hips and no significant correlation between bone attachment to the ‘pegs’ and bone area beneath the prosthetic cup was identified.

Discussion: From this study we have concluded that despite the resorption of bone beneath the prosthetic cup, the conservatve hip design investigated remained well fixed in the femur during the 1 year in vivo period. It appears that an implant design that resurfaces the femoral head with two pins used to transmit forces into the femoral neck is a useful approach in conservative hip design.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 368 - 368
1 Oct 2006
Aderinto J Blunn G
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Introduction: Bone marrow derived stromal stem cells (BMSSC’s) have the ability to differentiate into a variety of mesenchymal tissues including bone. The objective of this study was to evaluate the use a hydroxyapatite – BMSSC (HA-BMSSC) composite graft for posterior spinal fusion in a rabbit model.

Method: The HA- BMSSC composite graft was prepared by seeding rabbit marrow derived BMSSC’s onto 5 grams of HA granules which were cultured for a further 7 days prior to implantation. Bilateral posterior L4–L5 interlamina spinal fusion was performed using the HA- BMSSC composite graft (4 Rabbits), hydroxyapatite(HA) granules (6 rabbits) or autologous bone graft obtained from the iliac crest (6 rabbits). Rabbits were sacrificed at 5 weeks. Fusion was assessed by manual palpation. Quantitative histological analysis of cartilage, fibrous tissue and bone in the mid portion of the graft was performed using image analysis software.

Results: Three of four of the HA- BMSSC grafts fused successfully compared to 5 of 6 of the autologous bone grafts and 0 of 6 of the HA control grafts. The fusion rate was significantly higher in the iliac crest and HA- BMSSC groups than the HA control group (p< 0.05). In both the HA control and HA stem cell composite grafts there was ingrowth of new bone and encasement of HA granules by new trabecular bone at the graft – host interface. Within the mid region of the grafts there was bone formation in 2 of four fusion masses in the HA- BMSSC group comprising 26% and 45% of tissue in the area examined. In contrast bone formation was seen in the centre of only one of the six 6 HA fusion masses and amounted to only 2% of tissue. There was no significant difference in average percentage area of new bone, cartilage or fibrous tissue within the central region of the HA and HA-BMSSC grafts. There was a higher mean percentage area of new bone formation within the autologous bone graft (27%) than the HA control group (0.3%). p< 0.02.

Discussion: The BMSSC –HA composite was as effective as autologous graft and superior to HA in promoting fusion, but HA when used alone was ineffective. A positive finding to support the osteogenic potential of the stem cell loaded HA granules was the presence of moderate amounts of enchondral new bone isolated within the central regions of the graft away from the graft host interface in 2 of 4 fusion masses. In contrast the HA control grafts only supported significant amounts of bone formation in the periphery, adjacent to the host bed.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 363 - 363
1 Oct 2006
Marsh R Emeagi C Goodship A Amrich M Blunn G
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Introduction: The use of uncemented arthroplasty in joint replacement surgery requires osseointegration of the prosthesis to maximise function and longevity. It has been demonstrated that osteoblast-like cells will preferentially proliferate, differentiate and produce mineralised matrix in pits and grooves on non-biological surfaces, of similar dimensions to those of Howslip’s lacunae produced by osteoclasts in vitro. The hypotheses of this study were that a photochemically etched titanium alloy surface would 1) induce proliferation and differentiation in osteoblast-like cells; 2) induce osteoblastic differentiation of human mesenchymal stem cells and 3) induce greater bone to implant contact in a caprine model.

Methods: Three microgrooved titanium alloy surfaces (fine, medium & coarse) were created by photochemical etching, with dimensions of 200 to 515 microns. Human Mesenchymal stem cells (MSC) and Human Osteosarcoma (HOS) cells (TE-85) were seeded onto these surfaces and cultured in standard media; in the case of MSC, with and without the addition of osteogenic supplements. At intervals of time each surface and cell type were assessed for proliferation by Alamar blue assay and osteoblastic differentiation by Alkaline Phosphatase expression. A polished titanium surface was used as a control. A plate of each surface dimension was placed into a femoral condyle of ten adult male goats. The animals were euthanased at 6 and 12 weeks post-implantation. The specimens were histologically processed and examined under light and backscattered electron microscopy to establish the percentage of bone to implant contact and the presence of new bone within the grooves.

Results: In vitro, all cells showed an increase in proliferation with time, the greatest occurring on the coarse surface. Alkaline phosphatase expression showed a rise with time on all surfaces, the greatest being on the coarse surface seeded with HOS cells (p< 0.05). MSC could not be induced to differentiate to an osteogenic lineage by these surface textures alone. On addition of osteogenic supplements their results followed the trends of HOS cells. In vivo, histomorphometric analysis showed significantly greater bone implant contact on the coarse surface at both 6 and 12 weeks (p< 0.05). In a number of cases there were signs of osteogenesis occurring deep within the pits and grooves.

Discussion: This study confirms that a photochemically etched surface topography mimicking that created by osteoclasts will increase the proliferation and differentiation of osteoblastic cells in vitro. The rate of differentiation of these cells increased significantly in relation to the size of the grooves. When implanted in vivo these same surfaces were shown to support osseointegration. This surface has the potential to improve the function of uncemented arthroplasties in the future.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1367 - 1372
1 Oct 2006
Gupta A Pollock R Cannon SR Briggs TWR Skinner J Blunn G

We used a knee-sparing distal femoral endoprosthesis in young patients with malignant bone tumours of the distal femur in whom it was possible to resect the tumour and to preserve the distal femoral condyles. The proximal shaft of the endoprosthesis had a coated hydroxyapatite collar, while the distal end had hydroxyapatite-coated extracortical plates to secure it to the small residual femoral condylar fragment. We reviewed the preliminary results of this endoprosthesis in eight patients with primary bone tumours of the distal femur. Their mean age at surgery was 17.years (14 to 21). The mean follow-up was 24 months (20 to 31). At final follow-up the mean flexion at the knee was 102° (20° to 120°) and the mean Musculoskeletal Tumour Society score was 80% (57% to 96.7%).

There was excellent osteointegration at the prosthesis-proximal bone interface with formation of new bone around the hydroxyapatite collar. The prosthesis allowed preservation of the knee and achieved a good functional result. Formation of new bone and remodelling at the interface make the implant more secure. Further follow-up is required to determine the long-term structural integrity of the prosthesis.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 342 - 343
1 May 2006
Nguyen C Singh D Harrison M Blunn G Dudkiewicz I
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Introduction: Many mini compression screws are now available for fixation in procedures such as metatarsal osteotomies or arthrodeses of the foot.

The aim of the current study is to compare the compression forces achieved by the relatively new commercial mini compression screws on cortical and cancellous bone models.

Material and Methods: The screws that were tested are listed in the table below. All screws apart from the AO screws are headless and cannulated; and all screws apart from the AO cortical screw are self-tapping. The compression forces were tested by inserting a pressures load measurement cell between longitudinally-split sheep tibia as a cortical bone model and longitudinally split retrieved femoral heads as a cancellous bone model. The screws were inserted across the 2 halves with gradual compression after allowing the reading of the cell to settle.

Results: The Headed AO 3.5 mm cortical screw gave the best compression force, both in cortical and cancellous bone and the Bold was the weakest both in cortical and cancellous bone. The relative compression forces of the other tested screws were different between cortical and cancellous bone. Compression with the headless screws was lost as soon as the screw penetrated through the cortex in the cortrical bone model.

Conclusions: The indications for using headless self-tapping screws should be reserved for fixation of cancellous bone or of metatarsal or Akin osteotomies where compression is not required for union. When compression is important, such as in MPJ, tarso-metatarsal or talo-navicular arthrodeses, Headed AO 3.5 mm or 2.7 mm cortical or 4 mm cancellous screws, which give better compression, should be used.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 5 | Pages 649 - 654
1 May 2006
Gupta A Meswania J Pollock R Cannon SR Briggs TWR Taylor S Blunn G

We report our early experience with the use of a non-invasive distal femoral expandable endoprosthesis in seven skeletally immature patients with osteosarcoma of the distal femur. The patients had a mean age of 12.1 years (9 to 15) at the time of surgery. The prosthesis was lengthened at appropriate intervals in outpatient clinics, without anaesthesia, using the principle of electromagnetic induction. The patients were functionally evaluated using the Musculoskeletal Tumour Society scoring system. The mean follow-up was 20.2 months (14 to 30). The prostheses were lengthened by a mean of 25 mm (4.25 to 55) and maintained a mean knee flexion of 110° (100° to 120°). The mean Musculoskeletal Tumour Society score was 68% (11 to 29). Complications developed in two patients; one developed a flexion deformity of 25° at the knee joint, which was subsequently overcome and one died of disseminated disease. The early results from patients treated with this device have been encouraging. The implant avoids multiple surgical procedures, general anaesthesia and assists in maintaining leg-length equality.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 71 - 71
1 Mar 2006
Caruana J Mannan K Sanghrajka A Higgs D Briggs T Blunn G
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Introduction: Surgeons in the UK and Europe generally use a thinner cement mantle than their counterparts in the USA for the femoral component in total hip replacement. The aim of this study was to compare the performance of different thicknesses of cement mantle using finite element analysis. A linear-elastic model of the implanted femur is used to give a prediction of the stresses in the cement mantle and in the femoral cortex. These measures give an indication of cement cracking rates and stress shielding. To assess the reliability of our model in representing patients with different bone densities, we use a range of cancellous bone stiffnesses.

Method: Two cadaveric femora from the same donor were sized, reamed and implanted with identical Stanmore Hips. One was prepared using UK rasps, over-reaming by 2mm, the other using US rasps, over-reaming by 5mm. Serial CT-scans were used to create three-dimensional geometric models of the implanted femora. Two finite element meshes were hand-built in MSC.Marc finite element software, incorporating cortical and cancellous bone, bone cement and prosthesis, with a bonded stem-cement interface. Loading conditions were chosen to represent the heel-strike phase of gait. In order to assess the impact of variability in patient bone density, cancellous bone modulus was varied between 0.06 and 2.90 GPa.

Results: Equivalent stress was examined on the external surface of the cortex and the internal surface of the cement mantle. The lowest cortical bone stresses were proximal and the highest cement stresses around the distal tip of the prosthesis. In the proximal cortex, higher equivalent stresses were observed medially and laterally with a thick cement mantle. Distally, lower cement stresses were observed in the thick cement mantle. With the highest cancellous modulus, there was little difference between the two models. As this modulus was reduced, stress differences between the models became more apparent.

Discussion: Proximal stress shielding was greatest in the calcar, in agreement with clinical findings. The thicker cement mantle led to less stress shielding in this region. Cement stresses, highest around the distal tip of the prosthesis, were larger in the thin cement mantle. This suggests a higher rate of both cracking and bone resorption with thin cement mantles, particularly in patients with low bone density.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 34 - 34
1 Mar 2006
Rust P Blunn G Cannon S Briggs T
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Introduction Tissue engineering aims to produce a cellular structure in an extracellular matrix, which when implanted heals tissue defects.

To tissue-engineer bone suitable cells need to be grown on a scaffold. In this study we grew human marrow cells as they can differentiate into osteoblasts, on porous hydroxyapatite (HA) scaffolds, as this is osteoconductive, allows cell penetration and in growth of capillaries after implantation.

Increased extravascular perfusion through bone increases new bone formation. So we reproduced these physiological conditions in our novel bioreactor by perfusing scaffolds at 6ml/hr.

Hypotheses 1. Culture in our bioreactor improved cell penetration through HA scaffolds compared to static conditions. 2. Human mesenchymal stem cells (MSCs) cultured in our bioreactor differentiated into osteo-blasts and produced bone extracellular matrix.

Method MSCs were isolated from 8 human bone marrow aspirates taken from patients following informed consent. For each experiment 16 scaffolds were seeded with MSCs and comparisons were made between the two conditions. After 7 days culture the scaffolds were sectioned longitudinally and the number of cells at increasing depths were counted. The scaffolds were observed under SEM & TEM. Osteoblastic markers ALP and type I pro-collagen (PICP) were measured.

Results Penetration of cells through the scaffolds was significantly greater when cultured in the bioreactor.

After 14 days in bioreactor culture the HA was covered with cuboidal cells, consistent with osteoblasts, however in static culture cells remained fibroblastic. TEM results showed that MSCs in the bioreactor produced organised collagen matrix after 21 days and osteoid by 28 days, but no collagen matrix was observed following static culture.

ALP and PICP were significantly greater over 15 days culture when in our bioreactor.

Conclusions These results show that when MSCs were cultured in our bioreactor they attached and penetrated through porous HA scaffolds, whereas in static conditions few cells penetrated below 2mm. Our bioreactor significantly improved 3-dimensional growth, resembling tissue.

Moreover, MSCs grown on HA in the bioreactor produced significantly more ALP and PICP indicating osteoblastic differentiation. Furthermore, bone osteoid was produced.

Therefore this culture method could be use to convert autologous MSCs from human marrow into tissue-engineered bone which could be used to heal defects after tumor excision.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 190 - 190
1 Mar 2006
David L Blunn G Cannon S Briggs T
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Introduction: Total femoral endoprosthetic replacement can be an alternative to amputation following extensive tumour excision or in cases of severe bone loss. In skeletally immature patients the problem of leg length inequality may be overcome by the use of extendable prostheses. The aim of this study is to assess the functional outcome of patients following total femoral endoprosthetic replacement.

Methods: This is a retrospective, single centre study of 16 patients who underwent consecutive total femoral replacements between 1978 and 1999. Information was collected from the Bone Tumour database, medical records and clinical review. The prostheses were custom made by the Biomedical Engineering Department of University College London and Stanmore Implants Worldwide. The implants are composed of a Titanium alloy shaft with Cobalt-Chrome bearing surfaces, incorporating a SMILES (Stanmore Modular Individualised Lower Extremity System) knee joint. Outcome was assessed using the Musculoskeletal Tumour Society (MTS) rating score.

Sample: Eight patients were male and eight female. Mean age was 35 years (range 5–75 years). Ten patients underwent total femoral replacement as a primary procedure; nine for malignant tumour and one for hydatid disease. Of the patients with malignancy five had metastases at the time of presentation. The other indications were failed distal femoral replacement in four cases and periprosthetic fractures in the remaining two. Four children received extendable prostheses.

Results: Of the patients with malignant disease, all but one had complete tumour excision. Three patients developed local recurrence. Two patients died of metastases within one year of diagnosis and three more died within five years. Three required revision procedures. Two more dislocated at the hip joint. Other complications included infection and lymphoedema. In patients surviving longer than one year the average range of motion at the hip was 85 degrees and at the knee 80 degrees. Using the MTS rating score the mean functional outcome was 60% of normal (range 27–90%). Of the survivors one achieved an excellent result, five were good, four fair and one poor.

Conclusion: Total femoral endoprosthetic replacement can be effective in limb salvage and provide an alternative to amputation. Good functional results can often be achieved. However, the complication rate is high and the outcome extremely varied.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 97 - 97
1 Mar 2006
Lee J Maruthainar K Wardle N Haddad F Blunn G
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Introduction: Long term performance of total knee replacements is governed by wear of ultra-high molecular weight polyethylene (UHMWPE) which leads to aseptic loosening of the implant. Little has been done to reduce wear due to the femoral component properties in knee joint replacement. Scratching of the femoral component has been identified in retrieved knee replacements. Using a material that has a higher scratch resistance than current metals may reduce the rate of UHMWPE wear in knee replacements. In this study we investigated the effects of using an oxidized Zirconium femoral component has on wear in knee replacements.

Methods: Total knee replacements made of CoCr and oxidised zirconium were tested in a four station, six degrees of motion knee simulator for 4 million cycles. The surface roughness values (Ra, Rz and Sm) for the metal counterfaces was measured through the test. In addition gravimetric wear of the UHMWPE inserts was recorded. Scanning electron microscopy of the two counterface surfaces was performed to provide information on possible mechanisms involved in the wear process.

Results: The starting surface roughness for both CoCr and oxidised zirconium were similar (Ra=0.03m). Oxidised zirconium was significantly more scratch resistant than CoCr; Ra (mean average roughness) of 0.7m compared to 0.43m (p< < 0.01) at end of test, with similar differences in the other surface roughness parameters. This was accompanied by a 4 fold reduction in wear of UHMWPE 49.60mg to 12.48mg (p=0.02).

SEM analysis of the surfaces of the metals revealed large deep scratches of the CoCr implants which were aligned in the A-P sliding direction. Barium sulphate particles were seen embedded in the surface of the femoral component. Voids were seen in the surface of the cobalt chrome and particles of silicate polishing powder were seen in these voids. There was also evidence of scratches originating at these voids. By contrast oxidised zirconium, showed small amounts of superficial scratching with an intact surface and no evidence of third body particles.

Summary and conclusions: Oxidised zirconium leads to a reduction in wear of UHMWPE due to its increased resistance to third body wear. It has the potential to increase the longevity of total knee replacements by reducing wear of UHMWPE. Additionally, polishing powder used in the manufacture of cobalt chrome femoral components of knee joint replacements is a potential source of third body particles.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 355 - 355
1 Sep 2005
Dunstan E Sanghrahka A Tilley S Cannon S Blunn G Briggs T
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Introduction and Aims: Retrospective analysis of 25 consecutive metal-on-metal proximal femoral replacements performed at our unit between 1965 and 1979.

Method: Patients were clinically evaluated using the Modified Harris hip and Enneking Scoring Systems and radiologically evaluated using the ISOLOS scoring system. The concentration of Cr, Co, Ti, Al, V, Mo & Ni in whole blood and urine was also measured by High-Resolution Inductively Coupled Mass Spectrometry and compared with controls and patients with other implants.

Retrieved prostheses (in-situ for in excess of 25 years) were analysed for roughness and wear using a Mitutoya form tracer and an electron microscope.

Results: Thirteen patients have since died, nine from metastatic disease and four from other causes. Of the remainder, 11 (44%) are still alive, five still retaining metal-on-metal articulations and one has been lost to follow-up. They have been in-situ for an average of 32 years. The average modified Harris hip score is 76 (53–93) and the average Enneking Score is 74 (63–90).

In the retrieved prostheses the contact zones were found to be smoother (Ra 0.05mm), have fewer and smaller carbides, together with evidence of ‘self-healing’ when compared to the original surface (Ra 0.32mm).

Blood and urine levels of Co & Cr were significantly elevated. Co levels were exceptionally elevated in loose prostheses, but levels quickly fell following revision.

Conclusion: We have shown the potential longevity of metal-on-metal arthroplasty. The wear seen in retrieved specimens is low and we might expect to improve the fixation by reducing the torque with apical bearing and encouraging extra-cortical bone bridging with hydroxy-apatite-coated collars. Elevated serum and urine Co levels may well predict a loose prosthesis and may be useful as a screening tool.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 221 - 222
1 Sep 2005
Pendegrass C Oddy M Cannon S Goodship A Blunn G
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Introduction: Functional outcome following proximal tibial replacement can be impaired by extensor mechanism inefficiency. Current methods used to re-attach the patellar tendon result in varied levels of extensor function. Successful attachment of the patellar tendon requires initial mechanical stability and long-term biological fixation. We have employed a prosthesis, to model patellar tendon re-attachment, to test the hypothesis that biological augmentation of an implant which can provide sufficient mechanical integrity will allow a tendon-implant interface to develop that is similar in function and morphology to a normal tendon-bone interface.

Methods: The right patellar tendon in 24 Skeletally mature Friesland ewes was transfixed between the interlocking spikes of a hydroxyapatite-coated, customized tendon clamp to simulate patellar tendon re-attachment to a proximal tibial replacement. In 12 animals (Autograft group) the clamp attachment was augmented with autologous cancellous bone and marrow graft harvested from the ipsilateral iliac crest at the time of surgery, whilst the remaining animals (HA group) served as un-supplemented controls. Functional outcome was assessed using force plate measurements and two-dimensional optical kinematic gait analysis. Animals were euthanised at 6 and 12 weeks. The specimens were harvested, processed for histology and examined using light microscopy.

Results: The clamp device provided sufficient mechanical fixation of the patellar tendon to allow immediate weight bearing. Gait analysis showed that the range of movement of the stifle (knee) joint was not compromised by the surgical intervention at 6 or 12 weeks post-operation. An extensor lag observed at 6 weeks in both the Autograft and HA group was seen to fully recover by 12 weeks post-operation. There was a significant increase in functional weight bearing through the operated limb of the Autograft group animals between 6 and 12 weeks, which was not observed in the HA group. The tendon-implant interface in the HA group animals showed a fibrous tissue encapsulation of the HA coated surface, with collagen fibrils running parallel to the implant surface. In the Autograft group at 6 weeks post-operation a soft tissue – bone – HA interface had developed, similar in morphology to that of an indirect-type enthesis. Perpendicular orientated Sharpey’s-like fibres were observed spanning the region between the tendon and the HA coated implant and the bone graft material was seen to be undergoing active remodelling. By 12 weeks post-operation the interface was layered with regions of fibrocartilage clearly visible, more closely resembling the morphology of a direct-type enthesis.

Discussion: The clamp device provided sufficient mechanical fixation of the patellar tendon to allow immediate use the operated limb. The incorporation of a bio-active implant coating and biological augmentation encouraged a neo-enthesis to develop with near normal functional properties, and morphology similar to that of a normal patellar tendon-bone direct-type enthesis.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 222 - 222
1 Sep 2005
Fang S Coathup M Blunn G Goodship A
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Introduction: The aim of this study is to develop a novel approach to tissue engineering in vivo, in which the adaptive response of skeletal tissues to the imposed mechanical environment will be utilised to induce a cartilaginous resurfacing of the acetabular articulation in a hemi-arthroplasty model of hip replacement. Our hypothesis was that a cartilaginous resurfacing of subchondral bone can be induced by applying stresses of 0 to 3 MPa to the articular surface of the acetabulum. We used an ovine hemiarthroplasty model where the stresses on the acetabulum were engineered by using different femoral head sizes.

Methods: Three groups of six sheep received unilateral hip hemi-arthroplasties and were sacrificed 24 weeks post-operatively to harvest the acetabula. At operation, acetabular cartilage was removed completely and the subchondral bone was reamed down and left bleeding. Three femoral head sizes, 25, 28, and 32-mm, were used to induce different contact stress levels. Vertical ground reaction force (GRF) data were measured and normalised by body weight for both limbs pre-operatively and every 4 weeks post-operatively. Five specimens from each group and eight unoperated controls were processed and stained with Safranin O and Sirius Red. Cartilage proteoglycans in the regenerated tissues from four specimens in the 25-mm group were detected by immunoblotting using specific monoclonal antibodies.

Results: The operated limbs were subjected to an average of 80 to 90% pre-operative GRF after the eighth post-operative week and maintained till the end of the study. No significant difference was noted during the period between the three groups. A layer of regenerated tissue was noted on all specimens processed and was Sirius positive. Four operated specimens processed in the 25-mm group and three in the 28-mm group were Safranin O positive. The presence of cartilage aggrecan, cartilage link proteins, biglycan, and decorin was confirmed by immunoblotting.

Discussion and Conclusion: We conclude that a cartilaginous resurfacing of acetabulum can be induced in vivo under the mechanical environment imposed by our hemi-arthroplasty model. This approach may be advantageous in clinical practice as a regenerated acetabular cartilaginous surface would avoid the problems associated with wear of the plastic acetabular cup and replacement of the acetabulum.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 221 - 221
1 Sep 2005
Rust P Blunn G Cannon S Briggs T
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Introduction: The treatment of bone defects that occurs following fractures, the excision of bone tumours and at revision arthroplasty surgery, often involves the use of either autologous or allogenous bone grafts. However, both grafts have limitations. The aim of tissue engineering is to produce cells within an extracellular matrix that resembles tissue, which can be implanted into a patient to heal a tissue defect. The potential to engineer bone tissue grafts from patients’ autologous cells would improve the treatment of bone defects.

Bone marrow contains cells, known as mesenchymal stem cells (MSCs), which have the ability to differentiate into osteoblasts. To create a 3-dimensional structure necessary for the reconstruction of tissue, cells need to be grown on a scaffold, for which hydroxyapatite (HA) was used, as it is osteoconductive. In living bone, increased extravascular perfusion increases new bone formation. Thus, these physiological conditions were reproduced in our novel bioreactor by perfusing MSCs seeded on porous HA scaffolds at a rate of 6ml/hr. Hypotheses: 1. Culture in this bioreactor improves cell penetration through a HA scaffold. 2. MSCs cultured on HA in this bioreactor differentiated into osteoblasts.

Method: MSCs were isolated from 8 bone marrow aspirates, which were taken from patients during orthopaedic procedures following informed consent. For each experiment, MSCs from each patient were seeded onto 2 x 1cm3 scaffolds. To test cell penetration, the HA scaffolds were cultured for 7 days, then sectioned longitudinally and the number of cells were counted at increasing depths. Observations of MSCs on HA were compared under scanning (SEM) and transmission (TEM) electron microscopy. The HA scaffolds were cultured with MSCs in the bioreactor for 5, 10 & 15 days, after which time alkaline phosphatase (ALP) and type I pro-collagen protein levels were measured.

Results: Penetration of cells through the porous HA scaffold was significantly greater when the cells had been cultured in the bioreactor (P< 0.05). Observing MSCs after 7 days in bioreactor culture under SEM, adherent fibroblastic cells formed a network over the HA. However, by 14 days the HA was covered with cuboidal cells, consistent with osteoblasts. TEM results showed that MSCs cultured on HA in the bioreactor produced organised collagen matrix after 28 days. Osteoblastic protein levels were significantly greater at each time point when MSCs were cultured in bioreactor conditions: ALP (P< 0.005) and type I pro-collagen (P< 0.05).

Discussion and Conclusions: These results show that when cultured in our novel bioreactor, MSCs penetrated uniformly through the porous HA scaffold, whereas few cells penetrated in static culture conditions. Thus, our bio-reactor significantly improves the 3-dimensional growth of cells, resembling tissue. Moreover, in this study MSCs grown on HA in the bioreactor produced significantly larger amounts of ALP and type I pro-collagen, indicating that the MSCs differentiated into osteoblasts. Observations under TEM showed extracellular collagen matrix production which, when mineralized, produces bone.

Therefore, this culture method could potentially be used to convert MSCs, isolated from patients’ bone marrow, into tissue-engineered bone.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 222 - 223
1 Sep 2005
Rust P Kalsi P Blunn G Cannon S Briggs T
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Introduction: Bone grafts are frequently used in orthopaedic operations to augment bone healing. Autologous bone graft is the gold standard for osteogenesis, but the amount available from the patient’s iliac crest is often insufficient to fill the defect and donor site morbidity is a significant complication. Alternatively, allograft can be implanted into patients, however, processing is necessary to reduce the immunicity of the graft and the risk of transmission of infection, but this destroys osteoprogenitor cells and hence reduces the osteogenic properties of the graft. Mesenchymal stem cells (MSCs) are present in bone marrow and have the ability to differentiate into osteoblasts. Therefore our study examined the use of MCSs, from bone marrow, to enhance the osteogenic properties of allograft.

Hypothesis: MSCs cultured on freeze-dried ethylene oxide treated bone allograft differentiate into osteoblasts, thereby increasing the osteogenic nature of the graft material.

Method: After informed consent, bone marrow aspirates were taken from 10 patients during elective orthopaedic operations. MSCs were characterized using Stro-1 antibody and grown on freeze-dried ethylene oxide treated bone allograft in vitro.

The hypothesis was tested on three groups of graft, with eight samples in each group. Firstly, freeze-dried ethylene oxide treated bone graft was tested (group 2). For a negative control, allograft was heated to 70°C to denature the osteogenic proteins (group 1). The final group tested the effect of additional osteogenic supplements (100nM dexamethasone, 0.05mM ascorbic acid and 10mM (-glycerol phosphate) on MSCs on allograft (group 3).

Osteoblastic differentiation of MSCs was observed under scanning (SEM) and transmission (TEM) electron microscopy, and by measuring protein levels: alkaline phosphatase (ALP), osteopontin and type I pro-collagen over 14 days.

Results: SEM confirmed that MSCs could be successfully cultured on bone allograft. Cells grown in groups 2 and 3 were characteristic of metabolically active osteoblasts and collagen extracellular matrix was observed under TEM. The amount of ALP protein produced by MSCs cultured in groups 2 and 3 increased significantly over 14 days (P< 0.05), but there was no increase in group 1. ALP, osteopontin and type I pro-collagen production was significantly greater for group 2 than for group 1 and for group 3 than for group 2 (P< 0.05).

Discussion and Conclusions: ALP, type I pro-collagen and osteopontin proteins are known to be produced by osteoblasts during increasing cell maturation and the levels of each of these proteins increased significantly when MSCs were cultured on allograft for 14 days compared with the negative control. The addition of osteogenic supplements significantly increased production of these proteins. Furthermore, MSCs cultured in groups 2 and 3 produced extracellular collagen matrix. These results are consistent with allograft causing MSCs to differentiate into osteoblasts and that this differentiation increases with additional osteogenic supplements.

This study confirms that MSCs, derived from autologous bone marrow, could be used to increase the osteogenic potential of allograft, thereby increasing bony healing in patients.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 231 - 231
1 Sep 2005
Baghla D Angel J Siddique M McPherson A Johal P Gedroyc W Blunn G
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Background: Interventional MRI provides a novel non-invasive method of in-vivo weight-bearing analysis of the subtalar joint. Preceding in-vivo experimentation with stereophotogammetry of volunteers embedded with tantalum beads has produced valuable data on relative talo-calcaneal motion (Lundberg et al. 1989). However the independent motion of each bone remains unanswered.

Materials and Methods: Six healthy males (mean 28.8 years), with no previous foot pathology, underwent static right foot weight bearing MRI imaging at 0°, 15° inversion, and 15° eversion. Using identifiable radiological markers the absolute and relative rotational and translational motion of the talus and calcaneum were analysed.

Results and Discussion: Inversion: The calcaneum externally rotates, plantar-flexes and angulates into varus. The talus shows greater plantar-flexion with similar varus angulation, with variable axial rotation. Relative talo-calcaneal motion thus involves, 6° relative talar internal rotation, 3.2° flexion and no motion in the frontal plane. Concurrently the talus moves laterally on the calcaneum, by 6.5mm, with variable translations in other planes. This results in posterior facet gapping and riding up of the talus at its posterolateral prominence. Eversion: The calcaneum plantar-flexes, undergoes valgus angulation, and shows variable rotation in the axial plane. The talus plantar-flexes less, externally rotates, and shifts into varus. Relative motion in the axial plane reverses rotations seen during inversion (2.5° talar external rotation). The 8° of relative valgus talo-calcaneal angulation is achieved consistently through considerable varus angulation of the talus, in a direction opposite to the input motion. This phenomenon has not been previously reported. From coronal MRI data, comparative talo-calcaneal motion in inversion is prevented by high bony congruity, whereas during eversion, the taut posterior tibio-talar ligament prevents talar valgus angulation.

Conclusion: We have demonstrated that Interventional MRI scanning is a valuable tool to analysing the weight bearing motion of the talo-calcaneal joint, whilst approaching the diagnostic accuracy of stereophoto-gammetry. We have also demonstrated consistent unexpected talar motion in the frontal plane. Talo-calcaneal motion is highly complex involving simultaneous rotation and translation, and hence calculations of instantaneous axes of rotation cannot effectively describe talo-calcaneal motion. We would suggest that relating individual and relative motion of the talus / calcaneum better describes subtalar kinematics.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 628 - 631
1 May 2005
Dunstan E Sanghrajka AP Tilley S Unwin P Blunn G Cannon SR Briggs TWR

Metal-on-metal hip bearings are being implanted into younger patients. The consequence of elevated levels of potentially carcinogenic metal ions is therefore a cause for concern. We have determined the levels of cobalt (Co), chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of patients who had had metal-on-metal and metal-on-polyethylene articulations in situ for more than 30 years. We compared these with each other and with the levels for a control group of subjects.

We found significantly elevated levels of whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and urine levels of Co were grossly elevated, by a factor of 50 and 300 times respectively in patients with loose metal-on-metal articulations when compared with the control group. Stable metal-on-metal articulations showed much lower levels. Elevated levels of whole blood or urinary Co may be useful in identifying metal-on-metal articulations which are loose.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 534 - 539
1 Apr 2005
Cobb JP Ashwood N Robbins G Witt JD Unwin PS Blunn G

Massive endoprostheses using a cemented intramedullary stem are widely used to allow early resumption of activity after surgery for tumours. The survival of the prosthesis varies with the anatomical site, the type of prosthesis and the mode of fixation. Revision surgery is required in many cases because of aseptic loosening. Insertion of a second cemented endoprosthesis may be difficult because of the poor quality of the remaining bone, and loosening recurs quickly.

We describe a series of 14 patients with triplate fixation in difficult revision or joint-sparing tumour surgery with a minimum follow-up of four years. The triplate design incorporated well within a remodelled cortex to achieve osseomechanical integration with all patients regaining their original level of function within five months.

Our preliminary results suggest that this technique may provide an easy, biomechanically friendly alternative to insertion of a further device with an intramedullary stem, which has a shorter lifespan in revision or joint-sparing tumour surgery. A short segment of bone remaining after resection of a tumour will not accept an intramedullary stem, but may be soundly fixed using this method.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 3 | Pages 421 - 425
1 Mar 2005
Blom AW Cunningham JL Hughes G Lawes TJ Smith N Blunn G Learmonth ID Goodship AE

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery.

Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens.

There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 78 - 78
1 Mar 2005
Gupta A Sraals E Kochar T Blunn G Briggs T Cannon S
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Purpose- To review the long term survival of patients, complications and functional outcome of diaphyseal replacements in 40 consecutive femoral endoprosthetic reconstructions for treatment of primary bone sarcoma.

Methods- A retrospective case study analysis was performed on all patients treated in our hospital between 1991 and 2002 with diaphyseal replacements for the management of sarcomas of femur.

Results- 40 cases (28 males and 12 females) with a mean age of 38.4 years (10–56) were identified.The indications were ostesarcoma (18), chondrosarcoma (12), MFH (4) and ewings sarcoma (6). The presenting complaints were pain (24), swelling (16) or both (6). Fibular strut graft was used in 12 cases as an adjuvant to the diaphyseal replacement. Adequate surgical clearence was obtained in 37 cases (92.5%). The average follow up period was 98 months (11–158). The patients were assessed by the Musculoskeletal Tumour Society (MSTS) scoring system. The average MSTS score was 19 (range 16–22). The average range of motion at the knee was 94° (range 74°–126°). Twenty nine remained disease free at review. 16 patients died at a median of 28 months (11 to 124) – 6 from metastatic disease and 10 from other causes. The cumulative complication rate was 18%- wound debridement (5%), infection (3%), revision surgeries (10%–4 cases- periprosthetic fracture n=1, implant breakage n=1 and implant loosening n=2.) One patient needed amputation for recurrence.

Conclusion-.Surgical management of bone tumours using diaphyseal endoprosthesis is an effective method of treatment which allows the patient to retain a high level of function and range of motion.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 77 - 77
1 Mar 2005
Sanghrajka A Amin A Briggs T Cannon S Blunn G Unwin P
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Purpose: The purpose of this study was to determine whether the low rate of mechanical loosening of the SMILES rotating hinge distal femoral endoprosthesis relates to the hydroxyapatite (HA)-coated, grooved collar of the femoral component.

Methods and results: A database was used to identify two groups of cases of primary distal femoral replacement with a custom-designed and manufactured SMILES endoprosthesis at our unit; those with the collared femoral component (“collar group”), and those without a collar (“non-collar group”). From these two groups, patients were pair-matched for age and length of bone resection. We performed a retrospective review of serial biplanar pairs of radiographs of each patient, assessing radiolucent lines and extracortical bone pedicle. 11 matched pairs were identified, (14 females, 8 males), with a mean age of 36 years, (range 16–66). The pathology was primary bone tumour in 20 cases, (17 malignant, 3 benign), and metastatic disease in 2 cases. Mean length of follow-up was 85 months, (range 27–122). Radiolucent line score (RLS) progression over time was significantly lower in the collar group, (0.01 vs 0.73, p=0.001) (fig. 1 & 2), as was the mean final RLS, (2.72 vs 7.81, p=0.02). Mean RLS per radiographic quadrant was 0.56 in cases in which a bony pedicle was ingrown onto the prosthesis, (exclusively in the collared-group), 2.41 in cases in which the pedicle was not ingrown, (most prevalent in the non-collared group), and 1.02 in those cases without any pedicle formation, (ANOVA analysis, p=0.0002).

Conclusion: This study demonstrates that the HA-coated, grooved collar significantly reduces the progression of radiolucent lines, and consequently the overall RLS, explaining the reduced rate of mechanical loosening of the SMILES prosthesis. A bony pedicle that does not incorporate onto the prosthesis surface may be associated with an increase in radiographic loosening.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 76 - 76
1 Mar 2005
Gupta A Sood M Williams R Straal E Blunn G Briggs T Cannon S
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When managing malignant bone tumours in the distal femur with limb salvage, resection and reconstruction with a distal femoral replacement (DFR) conventionally entails prosthetic replacement of the knee joint. In younger patients it is desirable to try to preserve the knee joint. We now use a new Joint-Sparing distal femoral prosthesis in those cases where it is possible to resect the tumour and preserve the femoral condyles. Purpose of study: To look at our early results with knee joint preserving DFR’s. Methods: Between June 2001 and March 2004 the prosthesis was implanted in 8 patients (5 males and 3 females) aged between 8 and 24 years at the time of surgery. The diagnosis was osteosarcoma in 6 cases and chondrosarcoma in 2 cases. All patients were followed regularly and knee range of movement was recorded as well as any complications that occurred. Patients were functionally evaluated using the MSTS Scoring System. Results: Six of the patients had a mean follow-up of 20 months (range 8–33) and in this group 4 had good knee flexion with a mean flexion of 122° (110–130), 1 patient had fair flexion of 60° and 1 patient had poor flexion of 20°. The mean fixed flexion deformity in the 3 patients who had such a deformity was 10° (5–15). There were no intraoperative complications but the patient with poor flexion required an arthrolysis and because of the poor result is under consideration for conversion to a conventional DFR. Two patients had follow-up periods of 3 months or less and are still in their early rehabilitation period. One patient in this group developed sepsis that resolved after an open washout. Conclusions: Our early results with this prosthesis, in the patients with adequate follow-up, have been good in the majority but the two cases of fair and poor knee flexion are disappointing. This particular problem may relate to design and technical factors, which will be discussed in detail.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 76 - 76
1 Mar 2005
Sood M Gupta A Blunn G Meswania J Briggs T Cannon S
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When managing malignant long bone tumours in skeletally immature patients it is desirable, after resection, to reconstruct with a prosthesis that can be lengthened at appropriate intervals to keep pace with growth of the contralateral side. In an attempt to avoid multiple surgical procedures to achieve such lengthening we have recently developed a prosthesis that can be lengthened non-invasively.

Purpose of study: To look at our early experience with the use of non-invasive growing femoral prostheses.

Methods: Between November 2002 and February 2004 the prosthesis was implanted in 6 patients (3 males and 3 females) with a diagnosis of osteosarcoma. The patients were aged between 9 and 14 years (mean 11.5 years) at the time of surgery. Patients were lengthened at appropriate intervals and the process was monitored with scanograms. The prosthesis contains a magnet that is connected to gears that drive the extending mechanism. The patients’ limb is placed into a coil and the principle of electromagnetic induction coupling is used to achieve lengthening. Total degree of lengthening to date was recorded for each patient together with the range of knee movement and any complications that occurred. Patients were functionally evaluated at their last follow-up visit using the Musculoskeletal Tumour Society (MSTS) Scoring System.

Results: To date patients have been lengthened by an average of 18mm (8–48mm). The mean amount of knee flexion is 125 degrees. The mean MSTS score is 18 (16–21). There have been two complications; one patient developed patella subluxation during the lengthening programme and one patient has required serial casting to treat a flexion deformity of 25 degrees.

Conclusions: We have been encouraged by our early results with this prosthesis and have been able to demonstrate that the technology works reliably in vivo. We are continuing to use this prosthesis in skeletally immature patients.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 77 - 77
1 Mar 2005
Amin A Sanghrajka A Unwin P Blunn G Cannon SR Briggs T
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Purpose: The purpose of this study was to evaluate the results of custom-made endoprosthetic reconstruction for both tumourous and non-tumourous conditions around the elbow joint.

Methods and Results: 28 consecutive cases of endoprosthetic elbow reconstruction, performed between 1989 and 2003, were identified using the unit database. There were 12 males and 16 females, with a mean age of 48.9 years, (range 14–84). There were 16 cases of malignant tumour (10 primary, 6 secondary), 3 cases of benign tumour (one each of giant cell tumour, osteoblastoma and pigmented villonodular synovitis) and 10 non-oncological cases, (5 cases of fracture, 3 failed total elbow replacements and 1 infected synostosis). A distal humeral prosthesis was used in 16 patients, distal humeral and proximal ulna in 10 patients, proximal ulna with a humeral component in one patient and proximal radial replacement in one patient. Clinical and radiographic review of all available patients, including a functional assessment with The Toronto Extremity Salvage (TES) score was undertaken. The average follow-up was 54.9 months (range 5–144). 5 patients with malignancy died of their disease. One patient required amputation for local recurrence at 5 months. There were two revisions at 4 and 7 years for aseptic loosening of the humeral component. Six patients developed deep prosthetic infection at an average of 21 months (range 6–31), necessitating two-stage revision, of which one patient required subsequent excision arthroplasty. There were no cases of permanent nerve palsy. 18 patients (64.3%) were available for functional follow-up. Average flexion deformity was 33 degrees (7–80) and average flexion was 85 degrees (30–133). The mean TES score was 67.8 (range 36.6–96.6). The mean TES score following two-stage revision for infection, (available in 4/5 patients) was 73.9 (range 54.8–91.6).

Conclusion: Custom-made endoprosthetic reconstruction around the elbow joint is effective in a wide range of pathologies, allowing in most cases a reasonable level of function, even following two-stage revision for infection.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 267 - 271
1 Feb 2005
van Haaren EH Smit TH Phipps K Wuisman PIJM Blunn G Heyligers IC

Impacted morsellised allografts have been used successfully to address the problem of poor bone stock in revision surgery. However, there are concerns about the transmission of pathogens, the high cost and the shortage of supply of donor bone. Bone-graft extenders, such as tricalcium phosphate (TCP) and hydroxyapatite (HA), have been developed to minimise the use of donor bone. In a human cadaver model we have evaluated the surgical and mechanical feasibility of a TCP/HA bone-graft extender during impaction grafting revision surgery.

A TCP/HA allograft mix increased the risk of producing a fissure in the femur during the impaction procedure, but provided a higher initial mechanical stability when compared with bone graft alone. The implications of the use of this type of graft extender in impaction grafting revision surgery are discussed.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 250 - 250
1 Mar 2004
Biring G Meswania J Wylie C Muirhead-Allwood S Hua J Blunn G
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Aims: To investigate whether the use of mini-spigots result in enhanced wear and corrosion of tapers compared to standard spigots and the influence of the surface finish on this. Methods: The heads were cobalt chrome and the stems titanium alloy. Firstly wear and corrosion of standard spigots were compared with mini-spigots and secondly, these mini-spigots with another mini-spigot with a smoother surface finish. The samples were immersed in aerated Ringers solution (37°C) and loaded for 10 million cycles. Then samples were sectioned and the surface parameters measured and interfaces investigated using scanning electron microscopy. Static corrosion tests were used under loaded and non-loaded conditions and pitting tests for non-loaded samples. Results: Pre-experimentation the surfaces of the female tapers were similar for all heads. At the end of the first test the surface parameters on the female tapers had become significantly greater (p=0.034) for the mini-spigots compared with standard spigots and an abrupt change noted on the surface profile of the female taper where it contacted the male taper, indicating that the cobalt chrome head had corroded. Scanning electron microscopy showed that the coarser profile in the corroded region of the cobalt chrome head was similar to the profile on the titanium stem taper. Pitting corrosion was evident in the grooves on the cobalt chrome. The smooth mini-spigots were less affected. Conclusions: In cobalt chrome- titanium alloy combinations where the surface finish on the taper is coarse, corrosion is increased on a mini spigot compared with standard spigot. Surface finish is crucial and corrosion of the mini spigot is reduced if the surface finish is smooth.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 248 - 248
1 Mar 2004
Reddy V Siddique M Pinder I Blunn G
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Aims: To study functional outcome and survivorship of custom designed knee implants for primary and revision TKR where off-the-shelf prostheses were unsuitable. Methods: Clinical and radiological results of twenty-three custom-designed total knee prosthesis in twenty patients were prospectively reviewed. The indications were bone loss following multiple revisions of total knee prosthesis and debridement for infection, periprosthetic fractures, bone deformity with rickets and small bones with juvenile chronic arthritis. All implants designed and manufactured at Centre for Biomedical Engineering, Stanmore, U.K. Four different designs of knee prosthesis used: Condylar knee of miniature size, CAD-CAM knee, Superstabiliser and Rotating Hinges. Hospital for Special Surgery (HSS) score taken preoperatively, at 3 months, and yearly by an independent research physiotherapist. Duration of follow up: 62.5 months (28–126 months) Results: Average HSS score improved from 13.5 points (range 0–48) pre-operatively to 86.5 points postoperatively (range 62–96) (p=0.025). Average maximum flexion post operatively: 86.4° (range 60°–122°). Sixteen knees had excellent, five good and two poor results. Extension lag of 15°–25° in three patients. One patient with juvenile chronic arthritis needed revision at five years after index arthroplasty. Conclusions: Clinical and radiological results for custom designed prostheses compare favourably with standard knee prosthesis for similar indications. Our results support the use of a custom designed knee implant as salvage prosthesis and also as an alternative to arthrodesis or amputation.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 348 - 348
1 Mar 2004
Ashwood N Cobb J Robbins G Blunn G
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Massive cemented endoprosthesis are used to enable early resumption of activity after tumour surgery. The longevity of the prosthesis varies with anatomical site, pros-thesis type, and mode of þxation. Revision surgery will be required in approximately 50% of cases of endopros-thetic replacements around the knee by 10 years because of aseptic loosening. Insertion of a second cemented endoprosthesis is a challenge because of the poor quality of the remaining bone and loosening recurs quickly. The use of extracortical plate þxation in joint sparing surgery where the remaining bone after tumour resection will not accept an intramedullary stem is also described.

The þrst series of 14 patients with extracortical plate þxation in difþcult revision or joint-sparing tumour surgery with a mean follow-up of 5 years are described. The three-plate design incorporates well within a remodelled cortex to achieve osseomechanical integration with all patients regaining their premorbid level of function within 5 months. At 5 years the Enneking scores averaged 27.3.

One revision was required in a femoral replacement because of loosening. It was possible to insert a new endo-prosthesis as the intramedullary bone had reconstituted.

The preliminary results suggest that this technique may provide an easy, biomechanically friendly alternative to a device with an intramedullary stem, which has a shorter lifespan in revision tumour surgery.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 11 - 11
1 Jan 2003
Tingerides C Rust P Cannon S Briggs T Blunn G
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Mesenchymal stem cells (MSCs) are pluripotential cells present in marrow, which have the ability to differentiate into osteoblasts, chrondrocytes and adipocytes. Potential skeletal tissue engineering uses include healing bone defects, spinal fusion and revision arthoplasty surgery. A means of storing viable mesenchymal stem cells is necessary in order for these cells to be readily available for clinical use. The aim of this study was to determine whether cryopreservation has any effect on the osteogenic potential of human bone marrow derived MSCs.

Five normal iliac crest bone marrow aspirates were obtained following informed consent from patients. Each aspirate was divided into two equal samples. Ficoll-separation was used to isolate the MSCs. The fresh MSCs from one sample were cryopreserved, while the other was cultured as a control population. To assess the osteogenic potential of the MSCs after cryopreservation a sample of cells from each population was cultured with osteogenic supplements and the increase in alkaline phosphatase (ALP) and osteocalcin production was compared.

Cryopreservation was not observed to effect the primary cultures of MSCs, which became confluent after a similar period in culture (12–14 days), forming colonies with recognized MSCs morphology. The expression of ALP and osteocalcin after stimulating the MSCs to differentiate with osteogenic supplements, was not significantly altered by the cryopreservation process (P> 0.05).

In conclusion MSCs obtained from fresh human bone marrow aspirates can be cryopreserved without compromise to their proliferation rate or osteogenic potential, confirming that this is a useful means of storing viable cells for future clinical use.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 1 - 1
1 Jan 2003
Rust P Blunn G Cannon S Briggs T
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Osteoblast progenitor cells can be isolated from human bone marrow and on an appropriate carrier following differentiation into osteoblasts a bone block could be formed. This supply of autologous, osteoinductive bone graft substitute would have significant implications for clinical use. The aim of the study was to assess whether osteoblast progenitor cells isolated from human bone marrow, seeded onto porous hydroxyapatite (HA) blocks adhere, proliferate and differentiate into osteoblasts under the influence of HA alone.

After informed consent, bone marrow was aspirated from the iliac crest of 8 patients. The osteoblast progenitor cells were separated from the haematological cells and cultured in vitro. Evidence for the osteoblast progenitor nature of the cells was obtained by adding osteogenic supplements: dexamethasone, ascorbic acid and b-glycophosphate, and comparing alkaline phosphatase (ALP) and osteocalcin expression with that of unstimulated cells. Undifferentiated osteoblast progenitor cells were seeded at a density of 2x10 6 cells/porous HA cylindrical block (8 x 8 x10 mm). The cell adhesion to the HA was observed, and proliferation and ALP expression was measured over 15 days.

In monolayer culture the isolated bone marrow cells were morphologically identified as mesenchymal stem cells. When osteogenic supplements were added the phenotype became consistent with the morphology of osteoblastic cells, and the ALP expression was significantly higher (P< 0.05) after 5 days in culture compared with cells that had not been stimulated to differentiate.

On the HA osteoblast progenitor cells were adherent and became more osteoblastic, being separated from the HA surface by an osteoid matrix layer on electron microscopy. The ALP expression by these cells increased significantly (P< 0.05) over the 15 day culture period.

Bone marrow contains mesenchymal stem cells with osteogenic potential that are known as osteoblast progenitor cells. In this study we have shown that osteoblast progenitor cells can be isolated from human bone marrow and will adhere to and proliferate on HA blocks in vitro, and differentiate into osteoblasts spontaneously under the influence of the HA scaffold. These constructs could be used as osteoinductive bone grafts.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 14 - 14
1 Jan 2003
Ahir S Bayley J Walker P Squire-Taylor C Blunn G
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The restoration of pain-free stable function in gleno-humeral arthritic cases in various situations such as rotator cuff deficiency, old trauma and failed total shoulder arthroplasty is a challenging clinical dilemma. The Bayley-Walker shoulder has been designed specifically for very difficult cases where surface replacement devices do not provide sufficient stability. This device is a fixed-fulcrum reversed anatomy prosthesis consisting of a titanium glenoid component with a CoCrMo alloy head that articulates with an UHMWPE liner encased in a titanium alloy humeral component that has a long tapered grooved stem. The centre of rotation of the Bayley-Walker shoulder is placed medially and distally with respect to the normal shoulder in order to improve the efficiency of the abductor muscles. An important problem in devices of this type is obtaining secure and long-lasting fixation of the glenoid component. The glenoid component relies on fixation through the cortical bone by using threads, which protrude through the anterior surface of the scapula at the vault of the glenoid. It is HA coated for subsequent osseointegration. The purpose of this study was to investigate fixation of the glenoid component.

A 3D finite element model of the glenoid component implanted in a scapula was analysed using Abaqus. The implant was placed in position in the scapula, with the final 2–3 screw threads cutting through the cortical bone on the anterior side at the vault of the glenoid due to the anatomy in this region. The analysis was performed for two load cases at 60° and 90° abduction. A histological study of a retrieval case, obtained 121 days after implantation, was also conducted.

The FEA results showed that most of the forces were transmitted from the component to the cortical bone of the scapula, the remaining load being transmitted through cancellous bone. In particular the area where the threads of the glenoid component penetrated the scapula showed high strain energy densities. Histology from the retrieved case showed evidence of bone remodelling whereby new bone growth resulting in cortical remodelling had occurred around the threads.

Both the FEA and histological study show that fixing the component at multiple locations in cortical bone may overcome the problems of glenoid loosening associated with constrained devices. The Bayley-Walker device has been used on a custom basis since 1994; 81 Bayley–Walker shoulders for non-tumour conditions and 43 Bayley-Walker glenoid components have been used in association with a bone tumour implant, with good early results. Radiographically, radiolucencies have not been observed and overall the comparisons with the original Kessel design are positive.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 7 | Pages 946 - 949
1 Sep 2002
Blunn G del Preva EMB Costa L Fisher J Freeman MAR


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 195 - 195
1 Jul 2002
Pollock R Briggs T Cannon S Blunn G Pringle J
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The aim of this study is to evaluate the early results of gleno-humeral reconstruction after tumour excision with a new design of endoprosthesis.

The prosthesis is a fixed fulcrum gleno-humeral replacement consisting of a hydroxyapatite (HA) coated glenoid component with a polyethylene liner and a cemented stem with HA coated collar. Between 1997 and 2000 we inserted the prosthesis into 15 patients with primary bone tumours of the proximal humerus. There were nine males and six females with a mean age of 38 years (range: 8–71 years). Twelve stems were cemented and three uncemented. Two skeletally immature patients had an extendible stem inserted, one subsequently having a successful lengthening procedure. The mean follow-up was 28 months (range: 12–41 years). Functional outcome was assessed using the Musculoskeletal Tumour Society (MTS) scoring system.

There were two early dislocations and one superficial wound infection. Three patients died of their disease and one underwent forequarter amputation for local recurrence. The remaining eleven had satisfactory functional outcomes with a mean MTS score of 81%. Radiologically there has been no evidence of early loosening. Microscopic analysis of the components in the amputated arm showed excellent osseointegration around the HA coated components.


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 5 | Pages 795 - 801
1 Sep 1991
Jeffery A Blunn G Archer C Bentley G

The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair.