Aims

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

Lateral epicondylitis, or ’tennis elbow’, is a common condition that usually affects patients between 35 and 55 years of age. It is generally self-limiting, but in some patients it may continue to cause persistent symptoms, which can be refractory to treatment. This review discusses the mechanism of disease, symptoms and signs, investigations, current management protocols and potential new treatments.

Cite this article: Bone Joint J 2013;95-B:1158–64.

The aim of this study was to evaluate the role of peripheral blood derived mononucleated cells (PBMC) in osteochondral repair. We compared the healing of a critical size osteochondral defect in the medial femoral condyle and lateral trochlear sulcus in an ovine model.

Introduction

Massive rotator cuff repairs have up to 60% failure rate and repair of a chronic repair can have up to 40% failure rate. With this in mind, new methodologies are being to being developed to overcome this problem. The use of tendon augmentation grafts is one of them. Prior attempts have shown equivocal or poorer outcomes to control repairs. Aims and objectives: The specific aim of these expereiments was to test how well ovine tendon cells would take to a specific biological augmentation graft (Ligamimetic), and wheter tissue engineering techniques would enhance this.

Introduction

Rotator cuff tears remain a problem, with massive tears having a failure rate of repair reported of up to 60%, despite advances in surgical techniques. Tissue engineering techniques offers the possibility of regenerating damaged tendon tissue to a pre-injury state. We explore these techniques by implanting two novel tendon augmentation grafts with use of platelet rich plasma (PRP) in sheep.

Introduction

The MITCH PCR is an anatomic, flexible, horse-shoe shaped acetabular component, with 2 polar fins. The rationale of the PCR cup design is to reproduce a near-physiological stress distribution in the bone adjacent to the prosthesis. The thin composite cup is designed to fuse and flex in harmony with the surrounding bony structure. Only the pathological acetabular cartilage and underlying subchondral bone of the horseshoe-shaped, load-bearing portion of the acetabular socket is replaced, thus preserving viable bone stock. The PCR is manufactured from injection moulded carbon fibre reinforced polyetheretherketone (PEEK), with a two layer outer surface comprising hydroxyapatite and plasma sprayed commercially pure titanium. It is implanted in conjunction with a large diameter low wear femoral head, producing a bearing that will generate minimal wear debris with relatively inert particles.

Pre-clinical mechanical testing, finite element analysis and biocompatibility studies have been undertaken. FEA evaluation predicts preservation of host bone density in the load bearing segments. A pilot clinical study was completed on a proto-type version of the PCR cup (the “Cambridge” cup), achieving excellent 5 and 10 year results.

Mesenchymal stem cells (MSCs) have potential for therapeutic repair of cartilage and bone but still require optimization in terms of their capacity to deposit an appropriate extracellular matrix (ECM). Adult human cartilage has a limited capacity for repair and is unusual in that it is one of the few tissues where injury is not followed by an influx of monocytes. We are studying the effects of co-culturing primary monocytes with MSCs differentiating along chondrogenic lineage but in addition we needed to investigate the effects of the monocytes on the mature chondrocytes that will result from the MSCs and will also be present in the host tissue.

Human articular cartilage chondrocytes were isolated from human donors undergoing knee replacement surgery for osteoarthritis (OA) with full ethical consent. Cultures were expanded and cells used below passage five for co-culture experiments. Monocytes were prepared from fresh heparinized human blood samples by Ficoll gradient. Co-cultures consisted of either chondrocyte micromasses overlaid with monocytes, or chondrocytes and monocytes seeded together within a collagen/glycosaminoglycan scaffold (Chondromimetic, Tigenix UK). Media, cell pellets and scaffolds were analysed for extracellular matrix (ECM) proteins and proteases by dot blot, western blot, zymography and immunohistochemistry.

Human chondrocytes maintained stable micromasses and laid down an ECM for at least 40 days. Human monocytes eventually formed a proliferating cell population with a rounded morphology on top of the chondrocyte micromasses. These cells established an adherent population with a fibroblastic morphology when replated on plastic. Analysis of chondrocyte ECM proteins indicated that monocytes affected deposition of types I and II collagen, decorin and fibronectin and the overall amounts of gelatinases released. RTPCR demonstrated a decrease in type I collagen expression and a concomitant increase in MMP13 expression.

The precise interaction between monocytes and and chondrocytes has yet to be established but is thought to involve a mixture of contact and paracrine factors. In this study co-culture of monocytes with chondrocytes resulted in phenotypic changes to the chondrocytes which may warrant the inclusion of monocytes in cartilage/bone repair and also provide information as to the responses of OA chondrocytes to external stimuli.

Introduction

Mesenchymal stem cells (MSC) are an attractive cell population for regeneration of mesenchymal tissue such as bone and cartilage. Various studies have demonstrated the repair capacity of MSCs and even their usefulness in treating critical size defects. Much of the work conducted on adult stem cells has focused on MSCs found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. The aim of the present study is to evaluate the differentiation capability of adipose-tissue derived stem cells (ASC) extracted from the infrapatellar fat pad.

Porous collagen-glycosaminoglycan (Col/GAG) scaffolds have previously been used clinically as regeneration templates for peripheral nerves and skin^[1]. For defects involving even minimal load-bearing applications however, these scaffolds do not possess the required stiffness. Calcium phosphates (CaPs) are often used as bone-graft substitutes due to their biocompatibility and direct bone-bonding ability. While CaPs have sufficient stiffness for bone-defect applications, unlike Col/GAG they lack elasticity and are very brittle. Combining these two materials produces a composite with enhanced material properties and chemical similarity to natural bone. The addition of CaP nanocrystallites into the Col/GAG matrix produces a 3-dimensional structure that maintains its structural integrity even when wet. In this study, the in vivo performance of mineralised Col/GAG composites was evaluated by implantation into a six-week ovine bone-defect model.

Four different materials were implanted; Col/GAG alone, Col/GAG with octacalcium phosphate, Col/GAG with hydroxyapatite and Col/GAG with brushite. Implants with a diameter of 9mm and length of 9mm, were placed bilaterally into the distal femoral condyle of the hind legs of thirteen sheep. This site was selected due to the large volume of load-bearing cancellous bone. Cancellous autograft was harvested from the tibial tuberosity and placed in the defect sites of two sheep as a positive control.

All animals were sacrificed after 6 weeks and tissue containing the implants was prepared for histological evaluation. Image analysis of Von Kossa stained sections showed that all mineralised Col/GAG implants had significantly more bone in the implant site than unmineralised Col/GAG but were not significantly different between CaPs. Interestingly, new bone formation often followed the structure of the porous material struts which acted as a template. The defect containing the autograft contained the greatest amount of new bone.

Maintaining femoral neck cortical thickness may help prevent hip fracture. Fracture initiation probably starts superiorly at flaws, ie where the cortex is thinnest. Whole body computed tomography (QCT) is now being used to study cortical thickness but limited resolution (> 300 micrometers) makes in vivo estimates imprecise, whereas microscopy s resolution approaches 1 micrometer. We have therefore extended our microscopic studies on femoral neck biopsies to include men (14 cases, 26 controls) and women (50 cases, 23 controls), and here provide data on true cortical thickness in subjects with and without hip fracture.

Whole femoral neck cross-sections obtained at hemiarthroplasty (or at post-mortem in controls) were embedded in methacrylate, cut, stained and imaged at medium power. Image-J was used to define cortical boundaries and to measure cortical thicknesses at 5 degree intervals of arc from the cross-sections centre of area.

We confirmed that the mid-femoral neck (or narrow neck) site, defined as where the ratio of maximum to minimum neck diameter (max:min) is 1.4, shows great asymmetry, with the thick inferior cortical octant averaging over 3mm thickness (mean age 79 years inter-quartile range 74-85). In the superior 3 octants cortical thickness averaged 26% of that seen inferiorly. To assess statistical determinants of cortical thickness, the data were modelled with linear regression in octants after adjusting for subjects age, sex, max:min, and hip fracture status. To achieve normality of residuals the cortical thickness data were log-transformed. 95% of measured cortical thicknesses fell between 45% and 220% of the mean for octant. In the thinner, superior three octants, minimum thicknesses were just under 0.3 mm in the fracture cases ie close to 35% of the subjects mean for octant. Cases had about 17% thinner cortical thicknesses in all octants than controls, while female controls had cortical thicknesses that uniformly averaged 90% of male. In conclusion, compared to gender and age-matched controls, intra-capsular hip facture cases had generalized cortical thinning in all mid-neck octants. This disease effect contrasts markedly with the effect of normal ageing, which thins preferentially the mechanically under-loaded superior cortex and spares the infero-anterior cortex.

Meniscal cartilage provides joint stabilisation, load distribution, impact absorption and decreased friction in joints that have a complex movement such as the knee. If the meniscal cartilage degrades or is surgically removed, there is a strong probability, over time, of damage to the articular surface. The ability to regenerate damaged meniscal cartilage with an implanted device that replaces the biological equivalent would allow for joint stabilisation, robust movement and reduce the risk of damage to the articular cartilage. An implant with many of the characteristics of meniscus and with the ability to integrate correctly and firmly with the surrounding tissue, would be advantageous.

Inclusion of Platelet Rich Plasma (PRP) into the scaffolds to provide a concentrated source of matrix proteins and autologous growth factors may further enhance the regenerative repair process. To investigate the suitability of the collagen scaffolds, addition of meniscal chondrocytes and or PRP was examined in vitro.

Human meniscal chondrocyte cells were isolated, via collagenase digestion, from meniscal cartilage recovered from total knee replacement surgery. Meniscal chondrocytes were cultured in vitro to expand cell numbers. PRP was produced from volunteer's blood using a centrifuge and density based platelet recovery system. Release of Platelet Derived Growth Factor type AB (PDGF-AB) was measured by ELISA as an indicator of the behaviour of the peptide growth factor component. Combinations of scaffold, meniscal chondrocytes and PRP were tested for interaction, suitability and viability.

Experiments so far have shown good biocompatibility, in vitro, as meniscal chondrocytes were able to grow within the range of scaffolds produced. Cell retention could be enhanced by addition of PRP to the scaffolds. PDGF-AB was released over 5 days from the scaffold and PRP combination.

Further studies are in progress to derive relevant scaffold modifications and combinations for practical, robust, treatment strategies.

The aseptic loss of bone after hip replacement is a serious problem leading to implant instability. Hydroxyapatite coating of joint replacement components produces a bond with bone and helps to reduce loosening. However, over time bone remodeling at the implant interface leads to loss of hydroxyapatite. One possible solution would be to develop a coating that reduces hydroxyapatite and bone loss. Hydroxyapatite can be chemically modified through the substitution of ions to alter the biological response. Zinc is an essential trace element that has been found to inhibit osteoclast-like cell formation and decrease bone resorption. It was hoped that by substituting zinc into the hydroxyapatite lattice, the resultant zinc-substituted hydroxyapatite (ZnHA) would inhibit ceramic resorption and the resorption of bone. The aim of this work was to investigate the effect of ZnHA on the number and activity of osteoclasts.

Discs of phase pure hydroxyapatite (PPHA), 0.37wt% ZnHA and 0.58wt% ZnHA were produced, sintered at 1100 degrees Celsius and ground with 1200 grit silicon carbide paper. They were cultured in medium containing macrophage colony stimulating factor and receptor activator of nuclear factor kappa B ligand (RANKL) for 11 and 21 days. A control disc of PPHA cultured in medium containing no RANKL was also used. On the required dates the discs were removed and the cells stained for actin with phalloidin-TRITC and the cell nuclei with 4',6-Diamidino-2-phenylindole dihydrochloride. Cells with 3 or more nuclei were classed as osteoclasts and counted using ImageJ. On day 21 after the cells had been counted, the cells were removed and the discs coated in platinum before viewing with a scanning electron microscope. Resorption areas were then measured using ImageJ.

The addition of zinc was observed to significantly decrease the number of differentiated osteoclasts after 21 days (p<0.005 for 0.58wt% ZnHA compared to PPHA and p<0.01 for 0.37wt% ZnHA compared to PPHA). The area of resorption was also significantly decreased with the addition of zinc (p<0.005 for the comparison of 0.58wt% ZnHA with PPHA)

The work found that zinc substituted hydroxyapatite reduced the number and subsequent activity of osteoclasts.

Background

Mechanical trauma to articular cartilage is a known risk factor for Osteoarthritis (OA). The application of single impact load (SIL) to equine articular cartilage is described as a model of early OA changes and shown to induce a damage/repair response. Recombinant Human Fibroblast Growth Factor-18 (rhFGF-18) has been previously shown to have anabolic effects on chondrocytes in vitro. The aim of this in vitro study was to ascertain the effect of rhFGF-18 on the repair response of mechanically damaged articular cartilage.

Objectives

There is increasing application of bone morphogenetic proteins (BMPs) owing to their role in promoting fracture healing and bone fusion. However, an optimal delivery system has yet to be identified. The aims of this study were to synthesise bioactive BMP-2, combine it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide) (α-TCP/PLGA) nanocomposite and study its release from the composite.

In vitro femoral studies have demonstrated the addition of hydroxyapatite (HA), to morcellised bone graft (MBG) decreases femoral prosthesis subsidence. However, with an increased risk of femoral fracture during the impaction of a MBG:HA mixture, possibly due to greater force transmission to the femoral cortex via the HA. The aim was to compare the hoop strains and subsidence of a 1:1 mixture of MBG:HA with pure bone allograft during impaction and subsequent endurance testing in a revision hip arthroplasty model.

Materials and methods Large Sawbone femurs were prepared to represent a femur with bone loss (Sawbones, Sweden). 12 uniaxial strain gauges were attached to each femur at 0, 90, 180 and 270 degrees, at distal, midshaft, proximal points to measure hoop strain. Impaction grafting was performed using X-Change 2 instruments and an Instron servohydaulic machine for 2 distal impactions and 4 proximal impactions for 60 impactions each.

Introduction

The annual incidence of fractures in the UK is almost 4%. Bone grafting procedures and segmental bone transport have been employed for bone tissue regeneration. However, their limited availability, donor site morbidity and increased cost mean that there is still a large requirement for alternative methods and there is considerable research into regeneration using bone morphogenetic proteins (BMPs). The aims of this study are to synthesise and combine BMP-2 with a novel nanocomposite and study its release.

Problems associated with allograft are well known. The addition of hydroxyapatite (HA) to allograft has various mechanical advantages, especially within revision arthroplasty. The mixing of bone and HA results in mechanical properties different from the individual parts. However, at present the changes in material properties the mix have not been fully investigated and the optimum mixing ratio not characterized. A compressive uniaxial chamber was used to investigate the change in mechanical properties occurring with the addition of HA in varying proportions to morcellised bone graft (MBG).

Introduction

The purpose of this study was to investigate whether combining PRP or concentrated bone marrow aspirate (CBMA) with a biphasic collagen/glycosaminoglycan (CG) scaffold would improve the outcome of the treatment of full thickness osteochondral defects in sheep.

Introduction: Platelet rich plasma (PRP) has been hypothesised to be of potential benefit to articular cartilage tissue engineering, through its release of autologous growth factors. The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold.

Methods: Collagen/glycosaminoglycan scaffolds were fashioned, to which equal combined volumes of test substances were added (n=3): 500μl PRP; 375μl PRP + 125μl autologous thrombin (3:1); 455μl PRP + 45μl bovine thrombin (10:1). One ml of DMEM/F12 medium was added to each scaffold and changed completely at 12/24 hours, and 3/10 days, following which release of TGF-β1, PDGF-AB and bFGF were measured using ELISA. Secondly, equal sized collagen/glycosaminoglycan and polylactide co-glycolide scaffolds were fashioned to which 500μl of PRP were added (n=3). Similar conditions were followed as previously except that only PDGF-AB was assayed.

Results: A similar cumulative release profile of all growth factors was found over the 10 day period. An increase in growth factor release was seen in the PRP only group at all time points with PDGF-AB in particular reaching statistical significance at all time points (p< 0.006). These findings remained apparent when a correction for volume was made (p< 0.028) suggesting a particular role of the collagen in platelet activation. This was shown in the second experiment, in which a significantly increased cumulative volume of PDGF-AB was released from the collagen/glycosaminoglycan scaffold without thrombin activation (p< 0.04).

Discussion: This study shows that collagen is a potent activator of platelets, requiring no further addition to achieve satisfactory growth factor release when applied clinically. These results suggest that if PRP is combined with polymer scaffolds, it should be activated with thrombin to achieve optimum growth factor release.

Aims: Minimum ten year clinical, radiological and postmortem results of the flexible Cambridge Cup. This acetabular prosthesis was designed to replace the horseshoe shaped articular cartilage and provide physiological loading with minimal resection of healthy bone.

Method: Fifty female patients aged over 70 years with a displaced intra-capsular fracture of the femoral neck were recruited to the ethically-approved prospective study. They underwent implantation of the Cambridge Cup, which has an outer polybutyleneterephthalate shell and an inner UHMWPE bearing, with a Thompson-type hemiarthroplasty. The cups were manufactured with a 60μm plasma-sprayed coating of hydroxyapatite. This was removed from half the cups to simulate the effects of long-term HA resorption. Implants were sterilised by gamma irradiation in air. Independent clinical and radiological assessments were undertaken before discharge, at 6 weeks, one year, 18 months, two -, five-, seven- and ten years. Patients were scored using the Barthel Index, the Charnley-modified Merle d’Aubigne scores and latterly the Oxford hip score. The date and cause of death were obtained from hospital records and death certificates. Fifteen Cambridge Cups were retrieved post-mortem for histological and wear analysis

Results: The mean functional scores recovered to levels before fracture. These scores decreased with advancing age at five years. The mortality rates were 16%, 28%, 46% and 92% at 1, 2, 5 and 10 years. The Oxford hip scores in patients surviving between five and ten years were maintained.

The HA coated implants remained asymptomatic. Three uncoated components required revision for migration. No evidence of accelerated UHMWPE wear was seen on retrievals or radiographs. Histological analysis of the retrieved HA coated specimens showed excellent bony fixation, uncoated cups showed predominantly fibrous tissue.

Conclusion: The uncemented Cambridge Cup was implanted in a challenging environment of osteoporotic bone. Clinical, radiographic and post-mortem results up to ten years are excellent.

Introduction: Current treatment options for small, contained articular cartilage defects include microfracture, osteochondral autograft plugs or newer synthetic plugs. Chondromimetic is a novel biphasic biological scaffold composed of collagen and glycosaminoglycan. The addition of brushite provides the scaffold with a regionally specific component mimicking both phases of the osteochondral unit. The aim of this study was to show the efficacy of Chondromimetic in repairing a surgically created osteochondral defect in a caprine model.

Methods: Osteochondral defects were made in the lateral trochlear sulcus (LTS) and medial femoral condyle (MFC) of nine goats. Chondromimetic scaffolds (6x6mm) were inserted into each defect (n=6), while three controls had defects left empty (n=3). All animals were sacrificed at 26 weeks postoperatively. Macroscopic evaluations and quantitative stiffness properties were assessed. Histological sections were taken at approximately the centre of the defect, stained with Safrinin O/Fast Green and scored using a validated quantitative assessment tool.

Results: Macroscopically, the repair tissue scored higher in the MFC and LTS (p< 0.05) compared to controls. In all defects, the mechanical stiffness was found to be within one standard deviation of native cartilage, except that of the LTS controls. Histologically, the predominant tissue in the cartilage layer was deemed to be hyaline-like in three of six MFC defects, and five of six LTS defects according to the modified Sellers score. This was compared to one in three and zero of three in the MFC and LTS controls respectively.

Discussion: These results represent the early findings from an ongoing in-vivo study in which a further group of animals will be sacrificed at one year. At six months, the histology and mechanical properties are encouraging and should continue to improve with time. These results show that Chondromimetic may represent an acceptable alternative to marrow stimulation in the treatment of osteochondral defects.

Introduction: Platelet rich plasma (PRP) has been hypothesised to be of potential benefit to articular cartilage tissue engineering, through its release of autologous growth factors. The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold.

Methods: Collagen/glycosaminoglycan scaffolds were fashioned, to which equal combined volumes of test substances were added (n=3): 500μl PRP; 375μl PRP + 125μl autologous thrombin (3:1); 455μl PRP + 45μl bovine thrombin (10:1). One ml of DMEM/F12 medium was added to each scaffold and changed completely at 12/24 hours, and 3/10 days, following which release of TGF-β1, PDGF-AB and bFGF were measured using ELISA. Secondly, equal sized collagen/glycosaminogly-can and polylactide co-glycolide scaffolds were fashioned to which 500μl of PRP were added (n=3). Similar conditions were followed as previously except that only PDGF-AB was assayed.

Results: A similar cumulative release profile of all growth factors was found over the 10 day period. An increase in growth factor release was seen in the PRP only group at all time points with PDGF-AB in particular reaching statistical significance at all time points (p< 0.006). These findings remained apparent when a correction for volume was made (p< 0.028) suggesting a particular role of the collagen in platelet activation. This was shown in the second experiment, in which a significantly increased cumulative volume of PDGF-AB was released from the collagen/glycosaminoglycan scaffold without thrombin activation (p< 0.04).

Discussion: This study shows that collagen is a potent activator of platelets, requiring no further additive to achieve satisfactory growth factor release when applied clinically. These results suggest that if PRP is combined with polymer scaffolds, it should be activated with thrombin to achieve optimum growth factor release.

Introduction: Current treatment options for small, contained articular cartilage defects include microfracture, osteochondral autograft plugs or newer synthetic plugs. Chondromimetic is a novel biphasic biological scaffold composed of collagen and glycosaminoglycan. The addition of brushite provides the scaffold with a regionally specific component enabling the scaffold to mimic both phases of the osteochondral unit.

The aim of this study was to show the efficacy of Chondromimetic in repairing a surgically created osteochondral defect in a caprine model.

Methods: Osteochondral defects were made in the lateral trochlear sulcus (LTS) and medial femoral condyle (MFC) of nine goats. Chondromimetic scaffolds (6x6mm) were inserted into each defect (n=6), while three controls had defects left empty (n=3). All animals were sacrificed at 26 weeks postoperatively. Macroscopic evaluations and quantitative stiffness properties were assessed. Histological sections were taken at approximately the centre of the defect, stained with Safrinin O/Fast Green and scored using a validated quantitative assessment tool.

Results: Macroscopically, the repair tissue scored higher in the filled MFC and LTS (p< 0.05) compared to controls. In all defects, the mechanical stiffness was found to be within one standard deviation of native cartilage, except the LTS controls. Histologically, the predominant tissue in the cartilage layer was hyaline-like in three of six filled MFC defects, and five of six filled LTS defects according to the modified Sellers score. This was compared to one in three and zero of three in the MFC and LTS controls respectively.

Discussion: These results represent the early findings from an ongoing in-vivo study in which a further group of animals will be sacrificed at one year. At six months, the histology and mechanical properties are encouraging and should continue to improve with time. These results show that Chondromimetic may represent an acceptable alternative to marrow stimulation in the treatment of osteochondral defects.

Introduction: Platelet rich plasma (PRP) has been hypothesised to be of potential benefit to articular cartilage tissue engineering, through its release of autologous growth factors.

The aim of this study was to ascertain whether the addition of thrombin is required to achieve platelet activation and sustained growth factor release in-vitro, when PRP is applied to a collagen based osteochondral scaffold.

Methods: Collagen/glycosaminoglycan scaffolds were fashioned, to which equal combined volumes of test substances were added (n=3): 500μl PRP; 375μl PRP + 125μl autologous thrombin (3:1); 455μl PRP + 45μl bovine thrombin (10:1). One ml of DMEM/F12 medium was added to each scaffold and changed completely at 12/24 hours, and 3/10 days, following which release of TGF-β1, PDGF-AB and bFGF were measured using ELISA. Secondly, equal sized collagen/glycosaminogly-can and polylactide co-glycolide scaffolds were fashioned to which 500μl of PRP were added (n=3). Similar conditions were followed as previously except that only PDGF-AB was assayed.

Results: A similar cumulative release profile of all growth factors was found over the 10 day period. Greater growth factor release was seen in the PRP only group at all time points with PDGF-AB in particular reaching statistical significance at all time points (p< 0.006). These findings remained apparent when a correction for volume was made (p< 0.028) suggesting a particular role of the collagen in platelet activation. This was shown in the second experiment, in which a significantly increased cumulative volume of PDGF-AB was released from the collagen/glycosaminoglycan scaffold without thrombin activation (p< 0.04).

Discussion: This study shows that collagen is a potent activator of platelets, requiring no further addition to achieve satisfactory growth factor release when applied clinically. These results suggest that if PRP is combined with polylactide co-glycolide scaffolds, it should be activated with thrombin to achieve optimum growth factor release.

The influence of the timing of surgery for closed ankle fractures on complications is unclear. Previous studies have failed to demonstrate any associations with clear statistical support. This is a retrospective review of 221 patients presenting with closed ankle fractures treated with open reduction and internal fixation. The patients were similar in respect to age, gender, fracture type, surgeon grade, American Society of Anaesthesiologists grade, grade of anaesthetist and tourniquet time. Power analysis was performed for sample size. Patients were followed up until fracture union. The mean duration of inpatient care was greater in the delayed group (p = 0.0002). There was an increased rate of local (p = 0.0451) and total complications (p = 0.0116) if surgery was delayed more than 24 hours. This observational study demonstrates that for the management of closed ankle fractures there is an adverse clinical outcome in patients who undergo delayed operative intervention.

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model.

Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively.

After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.

There has been renewed interest in metal-on-metal bearings as hip resurfacing components for treatment in young, active patients. This study examines the effects of fixation (cemented or uncemented heads) and bone-implant interface conditions (stem-bone and head-bone) on the biomechanics of the Birmingham hip resurfacing (BHR) arthroplasty, using high resolution, 3-d computational models of the bilateral pelvis from a 45-year-old donor. Femoral bone stress and strain in the natural and BHR hips were compared. Bone remodelling stimuli were also determined for the BHR hips using changes in strain energy. Proximal femoral bone stress and strain were non-physiological when the BHR femoral component was fixed to bone. The reduction of strain energy within the femoral head was of sufficient magnitude to invoke early bone resorption. Less reduction of stress was demonstrated when the BHR femoral component was completely debonded from bone. Bone apposition around the distal stem was predicted based on the stress and strain transfer through the stem. Femoral stress or strain patterns were not affected by the type of fixation medium used (cemented vs. Uncemented). Analysis of proximal stress and strain shielding in the BHR arthroplasty provides a plausible mechanism for overall structural weakening due to loss of bony support. It is postulated that the proximal bone resorption and distal bone formation may progress to neck thinning as increasing stress and strain transfer occurs through the stem. This may be further exacerbated by additional proximal bone loss through avascular necrosis. Medium term retrieval specimens have shown bone remodelling that is consistent with our results. It is unclear if the clinical consequences of neck thinning will become more evident in longer-term follow-ups of the BHR.

One potential limitation with uncemented, hemispherical metal-backed acetabular components is stress shielding of bony structures due to the mismatch in elastic modulus between the metal backing and the peri-prosthetic bone. A proposed substitute is a horseshoe-shaped acetabular component, which replicates the bony anatomy. One such device, the Cambridge cup, has shown successful clinical and radiological outcomes at five years follow-up (Brooks 2004, Field 2005). We conducted a study of the Cambridge cup from a biomechanical perspective, using validated, high-resolution computational models of the bilateral hip. Peri-prosthetic stress and strain fields associated with the Cambridge cup were compared to those for the natural hip and a reconstructed hip with a conventional metal-backed hemispherical cup during peak gait loading. We found that the hemispherical cup caused an unphysiologic distribution of bone stresses in the superior roof and unphysiologic strain transfer around the acetabular fossa. These stress distributions are consistent with bone remodelling. In contrast, the peri-acetabular stresses and strains produced by the Cambridge cup differed from the natural hip but were more physiologic than the conventional hemispherical design. With the Cambridge cup, stresses in the superior acetabular roof, directly underneath the central bearing region, were greater than with the conventional design. Despite the thin bearing, the peak liner stresses in the Cambridge cup (max. tensile stress: 1.2 MPa; yield stress: 4.5 MPa) were much lower than the reported material strengths. Fossa loading by the hemispherical cup has been suggested as a possible mechanism for decreased implant stability (Widmer 2002). Conversely, the Cambridge cup produced semi-lunar peri-prosthetic stress fields, consistent with contact regions measured in natural hips (Widmer 2002). These analyses provide a better understanding of the biomechanics of the reconstructed acetabulum and suggest that a change in component geometry may promote long-term fixation in the pelvis.

Background: To analyse the effectiveness and complications of Less Invasive Stabilisation System (LISS plate) in the management of peri-prosthetic femoral fractures.

Materials and methods: We present a study of 18 peri-prosthetic femoral fractures around hip arthroplasty (16 females and 2 male patients) treated with LISS plate between September 2001 to February 2005. The average age of the patients was 81.6 years. Twelve patients had significant co-morbidities pre-operatively. All the fractures were classified according to the Vancouver classification for Peri-prosthetic fracture of femur. Ten were classified as type B1, two as type B2 and six as type C. Eleven fractures were around total hip replacement and seven were around hemi-arthroplasty (four cemented and 3 uncemented). Partial weight bearing started early post-operatively. Full weight bearing varied between 5-6 weeks depending on clinical and radiological status. The patients were followed up untill fracture union.

Results: Three patients died during the follow-up period owing to unrelated causes. The average follow up period was 11.7 months. All the remaining fifteen patients had satisfactory fracture union although one patient required further LISS plate following a fall 17 days postoperatively and another one patient developed low grade deep infection with a chronic sinus. It was noted that in one patient, plate had lifted off the bone at the proximal end with no loss of reduction of the fracture. Three patients were noted to have mild to moderate discomfort around the prominent implant. No implant breakage noted.

Conclusions: Even though LISS plate was originally designed for distal femoral fracture treatment, it appears to be very promising device in the treatment of peri-prosthetic femoral fractures (Type B1, Type C and medically unfit patients with Type B2 for stem- revision) with osteoporotic bone in elderly patients. Early mobilization is a key feature. This system involves minimally invasive approach, stable construct without need for primary bone grafting.

Prior studies have compared the bacterial load observed in laminar flow operating theatres (LFOTs) and standard operating theatres (STOTs) by wound culture and air sampling during surgery. However many organisms responsible for low grade infection after THR are not readily identified on routine culture and may be detectable only by more sensitive techniques such as the poly-merase chain reaction (PCR). This study assessed the wound contamination rate during THRs and compared the results in STOT with that in LFOTs using PCR.

We recruited patients undergoing primary THR for osteoarthritis. Surgery was performed in either STOTs or LFOTs, using identical skin preparation solutions, surgical drapes and operating attire. Specimens of the deep tissue, taken at the beginning and end of surgery, were each immediately separated into two sterile containers, one sent for culture (aerobic, anaerobic and enriched meat broth) and the other frozen at minus 80 degrees Celsius for PCR at a later date.

In each theatre type, 40 specimens from 20 THRs were analysed by both PCR and culture. Using PCR, bacterial DNA was identified on 12 of 40 specimens (30%) from STOTs, of which 3 were taken at the start of surgery and 9 at the end of the surgery, giving a 45% wound contamination rate (9 of 20). Two specimens (5%), both taken at the end of surgery, were positive on enriched culture. In LFOTs, bacterial DNA was identified by PCR on 8 of 40 specimens (20%), of which 2 were taken at the start of surgery and 6 at the end of surgery, giving a 30% wound contamination rate (6 of 20). No specimens were positive on enriched culture.

Wound contamination of primary THR occurs frequently in both STOTs and LFOTs. Although STOTs showed evidence of more frequent wound contamination than LFOTs, with the numbers available, no significant difference was detected. These data remind us the importance of aseptic surgical technique as significant wound contamination can occur despite the use of ultra clean air operating theatres.

Introduction: The Cambridge Acetabular cup is a unique, uncemented prosthesis that has been designed to transmit load to the supporting bone using a flexible material, carbon fibre reinforced polybutyleneterephthalate (CFRPBT). This should significantly reduce bone loss and provide long term stability. The cup consists of a ultra high molecular weight polyethylene liner within a carbon fibre composite backing that was tested with either a plasma sprayed HA coating or with the coating removed. The cup is a horseshoe shaped insert of similar thickness to the cartilage layer and transmits force only to the regions of the acetabulum originally covered with cartilage. The purpose of this study was to evaluate the response of bone and surrounding tissues to the presence of the cup in retrieved human specimens.

Methods: We examined 12 cementless Cambridge acetabular implants that were retrieved at autopsy between 2 and 84 months following surgery. Nine of the implants were coated with HA and three were uncoated. The implant and the surrounding bone were fixed, dehydrated and embedded in polymethylmethacrylate. Sections were cut parallel to the opening of the cup and in two different planes diagonally through the cup. The sections were surface stained with toluidine blue and examined by light microscopy. Image analysis was used to measure the percentage of bone apposition to the implant, the area of bone and fibrous tissue around the implant and the thickness of hydroxyapatite coating.

Results: All 9 HA coated implants showed good bone contact with a mean bone apposition and standard deviation of 50.9% +/− 17.5%. The thickness of the HA coating decreased with time and where this was occurring bone remodelling was seen adjacent to the HA surface. However, even in specimens where the HA coating had been removed completely good bone apposition to the CFRPBT remained. Bone marrow was seen apposed to the implant surface where HA and bone had both been resorbed with little or no fibrous tissue. The uncoated implants showed significantly less bone apposition than the HA coated specimens, mean 11.4% +/− 9.9%(p < 0.01) and significant amounts of fibrous tissue at the interface.

Discussion: The results of this study indicate that the anatomic design of the Cambridge Cup with a flexible CFRPBT backing and HA coating encourages good bone apposition. In the absence of HA the results are generally poor with less bone apposition and often a fibrous membrane at the implant surface. There was a decrease in HA thickness with time in situ and cell mediated bone remodelling seems to be the most likely explanation of the HA loss. However, good bone apposition was seen to the CFRPBT surface even after complete HA resorption in contrast to the uncoated specimens. Though the mean bone apposition percentage to the HA coated implants declined with time, the bone was replaced by marrow apposed to the implant surface. This is in contrast to the uncoated implants where fibrous tissue becomes apposed to the implant surface. We believe this is due to micro-motion occurring at the bone implant interface. The HA coating appears necessary to provide good initial bone bonding to the implant surface that is maintained even after complete loss of HA.

Introduction; In contrast to hydroxyapatite (HA), carbonate substituted hydroxyapatite (CHA) is resorbed by osteoclasts, and is more osteoconductive in vivo. On bone, osteoclastic resorption results not only in topographical changes, but also changes in the proteinaceous matrix within the resorption pit to which osteoblasts respond [1]. This study sought to investigate a possible link between the different bioresorptive properties of these biomaterials and subsequent bone formation on their surfaces, analogous to the coupling seen in normal bone remodelling.

Methods; Phase-pure HA and 2.7wt% CHA were prepared by aqueous precipitation methods [2] and processed into dense sintered discs for cell culture. Human osteoclasts derived from CD14+ precursors were cultured for 21 days on discs of HA and CHA; subsequently, cells and the proteinaceous layer were removed from some discs leaving a topographically altered surface (assessed by SEM and profilometry), whilst in others the proteinaceous layer was left intact. Control (unresorbed) discs were also prepared. The discs were then seeded with human osteoblasts (HOBs) which were cultured for up to 28 days, in some cases in the presence of hydrocortisone and â-glycerophosphate. Proliferation (MTS assay), collagen synthesis (3-H Proline incorporation), and the formation of mineralised nodules (tetra-cycline labelling [3] and SEM) were assessed.

Results; Osteoclasts altered the ceramic surfaces. Large pits were seen on CHA in contrast to limited erosion of the HA surface, accompanied by a greater increase surface roughness (Ra) (p< 0.05). After 6 days of culture, proliferation of HOBs was increased on resorbed discs provided the proteinaceous layer resulting from osteoclastic activity was left intact. At 28 days, cells had formed confluent sheets and there were no significant differences in their number. At 6 days, collagen synthesis by HOBs on CHA was increased on resorbed surfaces, and further increased if the proteinaceous layer was left intact. A similar response was seen on HA, but not until 28 days. Mineralised nodules formed after 28 days of culture in the presence of hydrocortisone and â-glycerophosphate on tissue culture plastic, but not in their absence. By contrast on the ceramics there was no evidence of mineralised nodule formation on any of the discs, although globular accretions were present in small amounts throughout the collagenous matrix regardless of the presence or absence of supplements.

Conclusion; Prior osteoclastic activity on HA and CHA affects subsequent proliferation and collagen production by HOBs. The effects of topographical alteration and matrix conditioning appear synergistic, and are apparent at an earlier time-point on a more resorbable ceramic. Osteoclastic activity may be important in the osteoconductive properties of biomaterials.

The effects of the method of fixation and interface conditions on the biomechanics of the femoral component of the Birmingham hip resurfacing arthroplasty were examined using a highly detailed three-dimensional computer model of the hip. Stresses and strains in the proximal femur were compared for the natural femur and for the femur resurfaced with the Birmingham hip resurfacing. A comparison of cemented versus uncemented fixation showed no advantage of either with regard to bone loading. When the Birmingham hip resurfacing femoral component was fixed to bone, proximal femoral stresses and strains were non-physiological. Bone resorption was predicted in the inferomedial and superolateral bone within the Birmingham hip resurfacing shell. Resorption was limited to the superolateral region when the stem was not fixed. The increased bone strain observed adjacent to the distal stem should stimulate an increase in bone density at that location. The remodelling of bone seen during revision of failed Birmingham hip resurfacing implants appears to be consistent with the predictions of our finite element analysis.

The Cambridge Cup has been designed to replace the horseshoe-shaped articular cartilage of the acetabulum and the underlying subchondral bone. It is intended to provide physiological loading with minimal resection of healthy bone.

The cup has been used in 50 women with displaced, subcapital fractures of the neck of the femur. In 24 cases, the cup was coated with hydroxyapatite. In 26, the coating was removed before implantation in order to simulate the effect of long-term resorption.

The mean Barthel index and the Charnley-modified Merle d’Aubigné scores recovered to their levels before fracture. We reviewed 30 women at two years, 21 were asymptomatic and nine reported minimal pain. The mean scores deteriorated slightly after five years reflecting the comorbidity of advancing age. Patients with the hydroxyapatite-coated components remained asymptomatic, with no wear or loosening. The uncoated components migrated after four years and three required revision. This trial shows good early results using a novel, hydroxyapatite-coated, physiological acetabular component.

Introduction: In the 1970’s, ‘viscosupplementation’ with hyaluronan was proposed as a potential treatment for OA with the idea that it would improve joint lubrication. However, despite studies showing its ability to reduce pain, the fact that the resident time within a joint (48 hours) is much less than its clinical effect (several months) along with pharmacological effects on chondroctyes and synoviocytes has confirmed that injected hyaluronan acts as a pharmaceutical rather than as a lubricant as originally thought. In this regard, the effects of inert synthetic lubricants on arthritic joints have not previously been adequately investigated.

This study examines the effect of injecting an inert synthetic lubricant, perfluoroalkylether (PFAE16350), as a mechanical joint lubricant to prevent the development of osteoarthritis in a surgically induced model of osteoarthritis in the adult guinea pig.

Materials & Methods: Osteoarthritic changes were initiated in the hind knee joint of 12 adult male Dunkin-Hartley guinea-pigs by excision of the medial meniscus and anterior cruciate ligament.

After wound closure, the animals were randomly assigned to 1 of 2 groups: (1) Single intra-articular injection of 1ml synthetic, sterile lubricant (PFAE16350) or (2) Control group with single intra-articular injection of 1ml 0.9% sterile saline.

At 9 weeks after surgery, after sacrifice, knee arthrotomy was performed, the presence of synthetic lubricant noted and the articular cartilages examined for macroscopic evidence of osteoarthritis. These cartilages were then fixed, embedded, sectioned, stained and graded histologically for osteoarthritis according to a modified Mankin scoring system.

Immunohistochemical studies were performed to assess for any inflammatory or cytotoxic effect by the lubricant.

Results: All guinea-pigs remained healthy and mobile throughout the study.

Subjective macroscopic assessment of the medial tibial plateau osteophyte was noted to be larger and the articular surface more roughened in the control cases compared to the lubricated cases. Synthetic lubricant was noted at arthrotomy in all cases where it was injected.

Guinea-pig joints treated with the synthetic lubricant showed a mean modified Mankin score of 3.0 points compared with the guinea-pig joints treated with saline where the median modified Mankin score was 8.5 points (p< 0.001). There was no evidence of an inflammatory or cytotoxic response by immunohistochemical studies.

Discussion: This study has confirmed that inert synthetic perfluoroalkylether lubricants can remain in the articular space for prolonged periods and inhibit the development of osteoarthritis without initiating an inflammatory response. Synthetic lubricants such as PFAE16350 warrant further investigation for potential use in osteoarthritis.

Introduction: Although there is evidence that laminar flow operating theatres (LFOTs) can reduce the incidence of wound infection over standard operating theatres (STOTs) when no routine peri-operative antibiotics were used, the evidence for the use with concurrent parenteral antibiotics is less compelling. A number of prior studies have compared the bacterial load observed in LFOTs and STOTs by wound culture and air sampling during surgery. However many organisms responsible for low grade infection after THR are not readily identified on routine culture and may be detectable only by more sensitive techniques such as the polymerase chain reaction (PCR), a molecular biology test for the presence of bacterial DNA. The purpose of this study was to compare the wound contamination rate during THRs performed in STOT with that in LFOTs using PCR.

Method: Patients undergoing primary THR for osteoarthritis without a history of joint infection were recruited for the study. Surgery was performed in either STOTs or LFOTs, using identical skin preparation solutions, surgical drapes and operating attire. Specimens of the deep tissue, taken at the beginning and end of surgery, were each immediately separated into two sterile containers, one sent for culture (aerobic, anaerobic and enriched meat broth) and the other frozen at minus 80 degrees Celsius for PCR at a later date.

Results: In each theatre type, 40 specimens from 20 THRs were analysed by both PCR and culture (80 specimens and 40 THRs in total).

Using PCR, bacterial DNA was identified on 12 of 40 specimens (30%) from STOTs. Of these 12, three were taken at the start of surgery and nine at the end of the surgery, equivalent to a 45% wound contamination rate (9 of 20). Only two specimens (5%), both taken at the end of surgery, were positive on enriched culture.

In LFOTs, bacterial DNA was identified by PCR on eight of 40 specimens (20%). Of these eight, two were taken at the start of surgery and six at the end of surgery, equivalent to a 30% wound contamination rate (6 of 20). None of the specimens were positive on enriched culture.

Discussions: We concluded that wound contamination of primary THR occurs frequently in both STOTs and LFOTs. Although STOTs showed evidence of more frequent wound contamination than LFOTs, with the numbers available, no significant difference was detected. These data are important in that they confirm that continued vigilance to technique continue to be important as significant wound contamination can occur despite the use of ultra clean air operating theatres.

Research is the quest for information. It is not an excuse for attending meetings in exotic places, nor is it an escape from clinical work that has become uninteresting. The early orthopaedic joumals contained reports of patients who have been treated by individual surgeons in specific, often novel, ways. There was little scientific structure, but nevertheless these papers were valuable as they disseminated knowledge to other Surgeons and also stimulated enquiry.

Orthopaedic research has developed dramatically over the last two or three decades. Patient related research has been advanced as a result of the availability of new techniques for example electron microscopy, DNA sequencing and the Genome, together with the discovery of the fine details of the cytokine control of cellular processes. This has gone hand in hand with the development of surgical sophistication allowing more adventurous interventions.

Joint replacement and internal fixation have led to close associations between orthopaedic surgeons and scientists from other disciplines, notably engineers and material scientists. This multi-disciplinary involvement is typical of orthopaedic surgeons and results in each discipline benefiting from the specialist knowledge of the others. The natural tendeney for orthopaedic surgeons to be interested in mechanical items is clear from a study of the distribution of interesting cars in the hospital car park!

The efficacy of different treatment methods should be challenged and this has resulted in the need for careful audit and epidemiological review. In some instances this has resulted in the conclusion that often used treatments are not effective. The assiduous application of the Cochrane principles is often very revealing, not least in that it indicates the lack of properly conducted orthopaedic trials.

Academic orthopaedics is in danger. In many countries the speciality is under pressure, normally as a result of economic measures that restrict the avallability of salarles and grants. In spite of these restrictions, it is surprising that there is a steady supply of excellent papers. How much better it could be with more funding.

The purpose of publícation is to share information. It should be the aim of every research worker to make a contribution to the understanding of the subject and to share his findings with his colleagues. Curiously many researchers feeI that their commitment to their project is complete as soon as they finish the trial and have the results. The preparafion of their work for dissemination through publication is often a very weak link and in some instances is absent. This is a dangerous tendency as their information may not be broadcast, wasting the scientific endeavour and endangering the status of the fundíng organisation, whose charitable status often depends on sharing the fruitg of research.

The incentive to publish is very variable. In some institutions the very existenee of a research department depends on a ‘paper score’ which is normally calculated from the product of the number of papers and the impact factor of the j ournal in which they are published. The calculation used to determine the impact factor of ajournal does not favour orthopaedic journals, as most orthopaedic papers are not quoted prolifically within the first year of publication. In contrast orthopaedic papers tend to have a much longer and more valuable lifetime and to some this is the more important and relevant feature. Unfortunately, the long-term value of the papers is not part of the calculation of impact factor. In order to achieve a high impact factor the publication must be in a rapidly changing field and contain at least a tiny element of special originality, which leads to it being quoted by most of the workers in that field. In the publishing world there is an ongoing discussion conceming an index that is more relevant than the impact factor.

For some, the competition for publication is so intense that there is ‘salami slicing’. Salami slicing is a process of publishing very small morsels of information in short papers instead of producing the complete study. It is done intentionally to increase the number of papers published and is frowned upon by scientific editors. Even worse there are cases of plagiarism and fraud, sadly occurring more commonly in surgical publication, than in other disciplines.

It may be time to ask fundamental questions about the need for research, articularly the need for every doctor in training to improve or embellish his or her Curriculum Vitae by decorating it with published works. There ís a tendeney for the more wealthy and better respected grant awarding bodies to fund successful rescarch teams, rather than to risk their limited resources on a spectacular project from an unknown team.

Funding is avallable from commercial sources. The role of this type of rescarch may require special assessment. There are issues of intellectual property rights and instances of commercial organisations delaymg or preventing publication if the findings of the study are not favourable. Many cynical readers give no weight to papers that are sponsored by commercial sources.

It is essential that rescarch in orthopaedics continues and that every possible step is taken in order to facilitate high quality research. There may be strength in numbers and it could be that the newly revitalised European Orthopaedic Research Society could help in supporting the endeavours of rescarch workers, particularly when it comes to European funding.

There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) in serum from patients who had sustained a head injury with and without fracture and compared these with levels found in control subjects.

Within 12 hours of injury the serum level of IL-6 was significantly higher in patients with head injury and fracture compared with the control group. Levels of IL-6 were also significantly higher in patients with head injury and fracture compared with fracture only. While there was no significant difference in circulating levels of sIL-6R in the initial samples they were increased one week after surgery in patients with head injury and fracture and with head injury only. In addition, reduced levels of sgp130 in patients with head injury with and without fracture indicated a possible reduction of the inhibitory effect of this protein on the activity of IL-6.

Our study suggests that IL-6 may be involved in altered healing of a fracture after head injury.

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFβ1 was absorbed on to a carrier of β tricalcium phosphate and Gelfoam® and used to fill a defect around a tibial implant in a rat model of revision arthoplasty.

We added 0.0, 0.02 μg, 0.1 μg or 1.0 μg of TGFβ1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed.

TGFβ1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of β TCP remaining in the tissue at any of the time points.

Aims: After Total Hip Replacement (THR), bearing surface pistoning during the gait cycle can affect wear rates. This ‘micro-separation’ has been shown clinically by video-fluoroscopy to be greater with a Metal-on-Polyethylene (MOP) bearing than a Metal-on-Metal (MOM) one. In this study, we quantified the suction forces that these bearings generate during the swing phase of the gait cycle as a result of interfacial tension from the thin fluid film present at the bearing surface. Methods: We used a servo-hydraulic universal testing machine with 250N load cell and programmed a sinusoidal waveform that could vary the loads and frequencies applied to MOP or MOM bearings submerged in 25% serum. We measured the bearing separation (±1μm) at tensile loads of 10N to 100N lasting 0.1s to 0.5s per 1Hz cycle.

Results: MOM bearings resisted tensile loads of up to 35N when applied for 0.1s to 0.5s of the simulated gait cycle. Bearing separation was measured at a maximum of 198 microns. Above 50N, the MOM bearing was unable to prevent separation occurring even when applied for only 0.1s of the simulated gait cycle (p< 0.001). The MOP bearing could not resist separation at any of the applied tensile loads (p< 0.0001).

Conclusions: The suction-fit of the MOM bearing used in this study is insufficient to prevent bearing separation due to gravity (110N). However, it may reduce the total bearing separation distance by delaying the time point at which separation occurs during the finite period of the swing phase (< 0.5s) during the gait cycle. This effect is crucially dependent upon the bearing clearance, bearing diameter, weight of the leg, speed of walking and soft tissue tension around the hip. This ultimately relies upon prosthetic design, patient selection and surgical technique.

Aim: Evaluate a novel horseshoe shaped cup designed by the senior authors to minimise the resection of healthy bone in total hip arthroplasty.

Method: Fifty female patients with a displaced, subcapital, femoral neck fractures were chosen for the study. In half of the group of patients, the composite support shell was coated with HA, with the other half remaining uncoated. Clinical and radiological assessments were undertaken regularly for 5 years.

Results: To date 20 patients have died and 13 have withdrawn from the study due to poor medical health unrelated to the study. Charnley modified Merle d’Aubigne score at 5 years was as good as the preoperative score with 80% of patients having full range of movement, no pain and walking unaided.

Radiographic results showed no evidence of loosening of HA coated cups, in contrast to non HA coated cups which migrated significantly in 80% of cases. Four patients with loose non HA coated cups underwent revision surgery.

Conclusion: It replaces the cartilage and underlying sub-chondral bone of the acetabulum socket with a cup that is designed to flex in harmony with the surrounding bony structure. This trial has demonstrated success at 5 years with the HA coated Cambridge Acetabular Cup. Cups from which HA coating has been removed have migrated significantly in 80% of cases. There is an advantage of the HA fixation which will be taken into account before wider clinical usage is advocated.

The novel horseshoe shaped cup was designed by the senior authors to minimise the resection of healthy bone in total hip arthroplasty. It replaces the cartilage and underlying sub-chondral bone of the acetabulum socket with a cup that is designed to flex in harmony with the surrounding bony structure.

Fifty female patients with a displaced, subcapital, femoral neck fractures were chosen for the study. In half of the group of patients, the composite support shell was coated with HA, with the other half remaining uncoated. Clinical and radiological assessments were undertaken regularly for five years.

To date 20 patients have died and 13 have withdrawn from the study due to poor medical health unrelated to the study. Charnley modified Merle d’Aubigne score at five years was as good as the preoperative score with 80% of patients having full range of movement, no pain and walking unaided.

Radiographic results showed no evidence of loosening of HA coated cups, in contrast to non HA coated cups which migrated significantly in 80% of cases. Four patients with loose non HA coated cups underwent revision surgery.

This trial has demonstrated success at 5 years with the HA coated Cambridge Acetabular Cup. Cups from which HA coating has been removed have migrated significantly in 80% of cases. There is an advantage of the HA fixation which will be taken into account before wider clinical usage is advocated.

Radio-pacifiers in bone cements are an accepted part of every-day practice. They have, however, been shown to be a potential cause of an increase in third body wear and to excite bone resorption in vitro and in vivo studies.

We reviewed the results of 228 consecutive Stanmore Total Hip Replacements performed between 1981 and 1985 in 211 patients. All were inserted with radiolucent bone cement. Information regarding whether the prosthesis had been revised was available for all patients. 73 patients (83 hips) were still alive and 41 patients (44 hips) were sufficiently healthy to attend clinic. Information regarding pain level was obtained from the remaining 32 patients. When revision of the implant was taken as the end-point, there was 95% ten-year survival, 91% fifteen-year survival and 75% eighteen-year survival. These long-term results of Stanmore THRs, performed in a district general hospital, with radiolucent bone cement, compare favourably with the other published series for this implant. We did not find the inability to see the bone cement a particular disadvantage when reviewing x-rays for signs of loosening.

Differentiating cases of aseptic loosening of total hip arthroplasty (THA) from loosening due to low-grade infection can often be difficult. It is possible that some cases of ‘aseptic’ loosening may be related to unidentified bacterial infection.

Using Polymerase Chain Reaction (PCR), this study attempted to identify the frequency with which bacterial DNA could be observed at revision arthroplasty for what was considered ‘aseptic’ loosening.

All revision cases had to fulfil strict criteria to be considered aseptically loose In all cases operative specimens from the synovial fluid, synovium, femoral and acetabular membranes where possible were sent for analysis by histology, bacteriology and by PCR to identify the presence of the 16S bacterial ribosomal fraction, an indicator of bacterial DNA. Ten bacteria per millilitre of tissue/fluid were the threshold for detection. As a control for environmental contamination, specimens from primary THA were also sent for analysis in the same manner as revisions.

The identification of bacterial DNA in at least one sample from a patient was considered a positive case result.

45 revision THA were identified over a 3-year period (1998–2001). From those 45 revision cases, 163 specimens were sent for analysis by PCR. These specimens were compared to the control group of 34 primary THA from which 91 specimens were sent for analysis by PCR. When analysed by specimens positive by PCR, bacterial DNA was identified in 55 of 163 specimens sent from the 45 revision THA. This compared with 21 of 91 specimens positive by PCR sent from the 34 primary THA (p=0. 07).

When analysed by cases positive by PCR, bacterial DNA was identified in 29 of 45 revision THA and in 8 of 34 primary THA (p< 0. 001).

PCR is a sensitive test for detecting infection in revision THA. Results from the primary THA cases would suggest there is at least a 23% false positive rate even with negative bacterial culture. The increased frequency with which bacterial DNA has been identified in ‘aseptically’ loose revision THAs, however, is unlikely to be due solely to environmental contamination. These results may have relevance for our interpretation and understanding of aseptic loosening as well for the diagnosis of prosthetic infection.

The use of musculo-skeletal MRI is increasing at spectacular rate, however there have been few rigorous evaluations of its’ clinical effectiveness. This study was conducted to assess the impact of MRI of the wrist on clinical diagnosis and patient management.

A controlled observational study was performed, in which referring clinicians completed questionnaires on diagnosis and intended management before and after wrist MRI. We analysed 118 consecutive patients referred for MRI of the wrist, to the magnetic resonance imaging units at a regional teaching hospital and a large district general hospital. We assessed: changes in clinicians’ leading and subsidiary diagnoses after MRI; their certainty of these diagnoses; and changes in intended patient management.

Five patients had incorrectly completed requests, ten cancelled their appointments and two could not tolerate the MR examination. Complete follow up data is available for 98/101 patients with correctly completed request forms who were examined. The clinical diagnosis changed in 55 of 98 patients (56%). Diagnostic certainty increased in 23 of the remaining 43 patients (53%). Clinicians reported that MRI had substantially improved their understanding of the patients’ disease in 67/98 (68%) patients. There was a change in management in 46/98 (47%) patients, with a shift away from operative treatment. 28 out of 98 (29%) patients were discharged without further investigation. MRI was similarly effective in a regional teaching centre and a district general hospital.

Magnetic resonance imaging of the wrist influences clinicians’ diagnoses and management plans. These results demonstrate the clinical effectiveness of MRI of the wrist in both a regional teaching centre and a district general hospital.

Introduction: Aseptic loosening of THR has a multifactorial aetiology. Differentiating such cases from loosening due to low-grade infection can often be difficult. It is possible that at least some cases of ‘aseptic’ loosening may be related to unidentified bacterial infection. This study attempted to identify the frequency with which bacterial DNA could be observed in the periprosthetic membrane and synovial fluid of patients undergoing revision surgery for what was considered ‘aseptic’ loosening.

Methods: Specimens from 39 revision and 31 primary hip replacements were obtained. The latter were used as a control for environmental contamination. All revision THR cases were investigated pre-operatively for infection by CRP, ESR, WCC, Gallium Scan. Operative specimens were analysed by bacteriological culture as well as by PCR to identify the presence of the 16S bacterial ribosomal fraction. Results were analysed by Chi square test.

Results: By PCR, bacterial DNA was identified in 22 of 39 revision hip surgery specimens and 6 of 31 primary hip replacement specimens (p=0.002). By culture none of these specimens had any bacterial growth.

Conclusions: The increased frequency with which bacterial DNA has been identified in ‘aseptically’ loose revision THR is unlikely to be due solely to environmental contamination although this remains a concern. These results may have relevance for our interpretation and understanding of aseptic loosening as well for the diagnosis of prosthetic infection.

There is evidence to suggest that fractures heal more rapidly in patients with a head injury as a result of systemic factors released from the site of this injury. We have measured the circulating level of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known involvement in the stimulation of the activity of osteoblasts and the healing of fractures.

The serum level of IGF-1 was significantly lower in patients with both head injury and fracture and fracture only compared with that in healthy volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also significantly lower in patients with both head injury and fracture (p < 0.01).

Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from week to week in both the patients and healthy control subjects. These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury.

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results.

Four different formulations of cement were found to be free from endotoxin using standard, gelclot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen.

Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin.

This study investigated the effects of wear particles, produced from a number of implant materials, at the bone-implant interface using a small animal model.

Particles were prepared from metal, ceramic and polymer replacement joint components or implant grade stock by grinding the materials against a diamond embedded grinding pad. The mean diameter of the particles ranged from 1.5mm to 3.2mm. Sterilised particles were suspended in sterile saline containing 2% v/v male Sprague-Dawley serum at a concentration of 109 particles per ml.

Seventy-two male Sprague-Dawley rats were assigned to twelve groups of six animals. A ceramic pin was inserted into the right tibia of each animal. Six groups were assigned a particle type with one group acting as vehicle control. 100ml of particle suspension or vehicle was injected into each knee joint at 8, 10 and 12 weeks following implantation and the animals were killed 2 weeks later. Of the remaining five groups, four were assigned a particle type and one was the vehicle control. These animals were injected with 100ml of particle suspension or vehicle at 20, 22 and 24 weeks following pin implantation and were killed 2 weeks later. The tibia and femora were removed, disarticulated and processed for histology. The total gap between pin and bone, including fibrous tissue, was measured.

Specimens showed no signs of infection either clinically or in the histopathology. All materials tested produced lesions at the bone-implant interface. A significant difference was seen between metal injected vs. vehicle control animals and aluminium oxide injected vs. vehicle controls. Particles of stainless steel produced the greatest response and this finding may have implications for the use of metal on metal articulations aimed at eliminating polyethylene wear.

This study investigated the relationship between histological, clinical and radiological features of aseptically loose total joint replacements (TJRs) and synovial fluid levels of interleukin (IL)-1b, IL-6, IL-8 and IL-10.

Tissue and synovial fluid samples were retrieved from patients undergoing primary (hip; n=15: knee; n=13), or revision of aseptically loose TJRs (hip; n=14: knee; n=9). The presence of inflammatory cells, blood vessels and wear debris in the tissue were assessed on a relative scale. Revision TJRs were assessed for sepsis, migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in the synovial fluid samples were determined by ELISA.

All cytokines were increased in synovial fluid from revision TJRs compared to primary replacements, as were the degree of macrophage and giant cell infiltration (p< 0.01). There was a significant positive correlation between the presence of macrophages and giant cells with the levels of IL-1b, IL-8 and IL-10 (p< 0.05) but not IL-6.

The amount of wear debris was related to the presence of macrophages and giant cells (p< 0.01) but not to any of the cytokines.

There were no relationships between any of the clinical parameters and the presence of wear debris or the levels of any cytokine with the exception of IL-6 and gross loosening (p< 0.01). Similarly there were no differences between hips and knees for any of the parameters except IL-6, for which higher levels were found in hips (p< 0.05).

The results suggest that macrophages and giant cells are responsible for the majority of IL-1b, IL-8 and IL-10 production but another cell type is contributing to IL-6 production. Furthermore, IL-6 does not fit the pattern of the other cytokines as it is upregulated in hip joints compared to knees and correlates with the presence of gross loosening. This may suggest a unique role for IL-6 that requires further investigation.

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO₂) and with barium sulphate (BaSO₄). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10⁹ particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis.

All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO₄-containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO₄ is used as the radiopaque agent.

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO₄, Palacos R with ZrO₂ and from CMW3 which contains BaSO₄. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis.

We have investigated whether the thigh tourniquet used during total knee replacement (TKR) influenced the development of postoperative wound hypoxia and was a cause of delayed wound healing.

We allocated randomly 31 patients (31 TKRs) to one of three groups: 1) no tourniquet; 2) tourniquet inflated at low pressure (about 225 mmHg); and 3) tourniquet inflated to high pressure of about 350 mmHg. Wound oxygenation was measured using transcutaneous oxygen electrodes.

In the first week after surgery, patients with a tourniquet inflated to a high pressure had greater wound hypoxia than those with a low pressure. Those without a tourniquet also had wound hypoxia, but the degree and duration were less pronounced than in either of the groups with a tourniquet.

Use of a tourniquet during TKR can increase postoperative wound hypoxia, especially when inflated to high pressures. Our findings may be relevant to wound healing and the development of wound infection.

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10⁴, 10⁶ or 10⁸ high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined.

Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05).

Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10⁸ particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process.

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells.

We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression.

Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo.

In ten male rats we inserted ceramic ‘drawing-pin’ implants in weight-bearing positions within the right proximal tibia. Two animals were killed 6 weeks after surgery and two more 14 weeks after surgery. The remaining six received intra-articular injections of either high-density polyethylene (4 rats) or saline (2 rats) at 8, 10 and 12 weeks after surgery. These animals were killed two weeks after the last injection.

Histological examination of the bone-implant interface in the control animals showed appositional bone growth around the implant at both 6 and 14 weeks. Polyethylene, but not saline, caused a chronic inflammatory response with numerous foreign-body giant cells in periprosthetic tissues.

Our model of a stable, weight-bearing bone-implant interface provides a simple and reliable system in which to study in vivo the effects of particulate materials used in orthopaedic surgery.

We measured bone mineral density (BMD) in the proximal femur by dual-energy X-ray absorptiometry (DEXA) in 20 patients after cemented total hip arthroplasty over a period of one year. We found a statistically significant reduction in periprosthetic BMD after six months on the medial side and on the lateral side adjacent to the mid and distal thirds of the prosthesis. At one year after operation there was a mean 6.7% reduction in BMD in the region of the calcar and a mean 5.3% increase in BMD in the femoral shaft distal to the tip of the implant. These changes reflect a pattern of reduced stress in the proximal femur and increased stress around the tip of the prosthesis. They support current concepts of bone remodelling in the proximal femur in response to prosthetic implantation.

Dual-energy X-ray absorptiometry (DEXA) is increasingly used to measure changes in bone mineral density (BMD) around femoral prostheses after total hip arthroplasty. We have studied the factors which affect the accuracy of these measurements. The coefficient of variation was < 2% using a hydroxyapatite phantom, 2.7% in an anthropomorphic phantom specimen, and < 1% in repeated measurements on implanted cadaver femora. The precision did not vary with different implant materials or designs. In patients we found a mean precision error of 2.7% to 3.4%. The most significant factor affecting reproducibility was rotation of the femur. We conclude that DEXA is a precise method of measurement for small changes in BMD around femoral implants, but that correct and careful positioning of patients is essential to obtain reliable results.

We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene.

We compared the mechanical properties of carbon fibre composite bone plates with those of stainless steel and titanium. The composite plates have less stiffness with good fatigue properties. Tissue culture and small animal implantation confirmed the biocompatibility of the material. We also present a preliminary report on the use of the carbon fibre composite plates in 40 forearm fractures. All fractures united, 67% of them showing radiological remodelling within six months. There were no refractures or mechanical failures, but five fractures showed an unexpected reaction; this is discussed.

We investigated the possibility that the macrophages which are seen around implants may stimulate bone resorption and cause loosening. We found that macrophages release mediators that stimulate bone resorption, and that the amount of resorption increased by between 2.5 and 10 times when the macrophages adhered to a foreign surface. This bone resorption depended on the surface energy and roughness of the foreign surface, varying with these physical properties rather than with the chemical nature of the material. It is concluded that loosening of orthopaedic implants is likely to be influenced by the surface energy and roughness of the implant.

Osteonecrosis of the femoral head is a severely disabling complication of steroid immunosuppression in renal transplant patients. We report 31 total hip arthroplasties in 21 renal transplant recipients with an average follow-up of six years. There were no problems with wound healing or infection despite full immunosuppression. Four hips developed symptomatic loosening but the other results were excellent, comparing well with other methods of treatment for osteonecrosis. Ten patients died during the follow-up period. Total hip replacement is a safe and effective treatment for transplant recipients and, in view of their limited life expectancy, should be considered at an early stage in their treatment.

A prospective study was made over a three-year period of 900 consecutive unilateral Colles' fractures. The radiographic features at the time of fracture, after reduction and one week later were measured and correlated with grip strength and range of movement at three years. The most significant radiographic feature to influence the outcome was the presence of shortening of the radius one week after reduction of the fracture. Persistent dorsal tilt, radiocarpal joint involvement and ulnar styloid fracture were each associated with reduced range of movement, but had no effect on grip strength. Extension of the fracture into the distal radio-ulnar joint was associated with reduced grip strength but had no effect on range of movement. Radial tilt of the radial fragment did not correlate with any aspect of the result after three years.

Thirty-nine patients underwent reconstruction of the anterior cruciate ligament with carbon-fibre and a MacIntosh repair; all had a negative pivot shift test after operation. Some patients had persistent pain, mild effusion and synovial thickening; in 10 of these patients the symptoms warranted arthroscopic examination and biopsy at a mean of 16.9 months after the repair. Arthroscopy revealed that the carbon-fibre had not induced the formation of a "new ligament" and that the repair was merely covered by a thin, fibrous sheath. Histological investigations confirmed this finding, with only a suggestion of a fibroblastic response to carbon-fibre found in two patients. Particles of carbon-fibre were found scattered through the knees. Synovitis and breakdown of the skin over subcutaneous carbon-fibre complicated treatment. Failure of the carbon-fibre to bond to bone was detected radiographically.