Dislocation remains a major concern after total hip replacement, and is often attributed to malposition of the components. The optimum position for placement of the components remains uncertain. We have attempted to identify a relatively safe zone in which movement of the hip will occur without impingement, even if one component is positioned incorrectly. A three-dimensional computer model was designed to simulate impingement and used to examine 125 combinations of positioning of the components in order to allow maximum movement without impingement. Increase in acetabular and/or femoral anteversion allowed greater internal rotation before impingement occurred, but decreases the amount of external rotation. A decrease in abduction of the acetabular components increased internal rotation while decreasing external rotation. Although some correction for malposition was allowable on the opposite side of the joint, extreme degrees could not be corrected because of bony impingement.

We introduce the concept of combined component position, in which anteversion and abduction of the acetabular component, along with femoral anteversion, are all defined as critical elements for stability.

We have investigated the anatomy of the proximal part of the ulna to assess its influence on the use of plates in the management of fractures at this site. We examined 54 specimens from cadavers. The mean varus angulation in the proximal third was 17.5° (11° to 23°) and the mean anterior deviation 4.5° (1° to 14°). These variations must be considered when applying plates to the dorsal surface of the ulna for Monteggia-type fractures. A pre-operative radiograph of the contralateral elbow may also be of value.

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal.

Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis.

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft.

A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r² = 0.867, p < 0.01) and also between its thickness (r² = 0.826, p < 0.01) and bone mineral density (r² = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378).

We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone.

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10⁷ AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10⁷ naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.

The complications of impaction bone grafting in revision hip replacement includes fracture of the femur and subsidence of the prosthesis. In this in vitro study we aimed to investigate whether the use of vibration, combined with a perforated tamp during the compaction of morsellised allograft would reduce peak loads and hoop strains in the femur as a surrogate marker of the risk of fracture and whether it would also improve graft compaction and prosthetic stability.

We found that the peak loads and hoop strains transmitted to the femoral cortex during graft compaction and subsidence of the stem in subsequent mechanical testing were reduced. This innovative technique has the potential to reduce the risk of intra-operative fracture and to improve graft compaction and therefore prosthetic stability.

We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant.

Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect.

Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans.

A cadaver study using six pairs of lower limbs was conducted to investigate the accuracy of computer navigation and standard instrumentation for the placement of the Birmingham Hip Resurfacing femoral component. The aim was to place all the femoral components with a stem-shaft angle of 135°.

The mean stem-shaft angle obtained in the standard instrumentation group was 127.7° (120° to 132°), compared with 133.3° (131° to 139°) in the computer navigation group (p = 0.03). The scatter obtained with computer-assisted navigation was approximately half that found using the conventional jig.

Computer navigation was more accurate and more consistent in its placement of the femoral component than standard instrumentation. We suggest that image-free computer-assisted navigation may have an application in aligning the femoral component during hip resurfacing.

Finite element analysis was used to examine the initial stability after hip resurfacing and the effect of the procedure on the contact mechanics at the articulating surfaces. Models were created with the components positioned anatomically and loaded physiologically through major muscle forces. Total micromovement of less than 10 μm was predicted for the press-fit acetabular components models, much below the 50 μm limit required to encourage osseointegration. Relatively high compressive acetabular and contact stresses were observed in these models. The press-fit procedure showed a moderate influence on the contact mechanics at the bearing surfaces, but produced marked deformation of the acetabular components. No edge contact was predicted for the acetabular components studied.

It is concluded that the frictional compressive stresses generated by the 1 mm to 2 mm interference-fit acetabular components, together with the minimal micromovement, would provide adequate stability for the implant, at least in the immediate post-operative situation.

We undertook a study on eight arms from fresh cadavers to define the clinical usefulness of the lesser sigmoid notch as a landmark when reconstructing the length of the neck of the radius in replacement of the head with a prosthesis. The head was resected and its height measured, along with several control measurements. This was compared with in situ measurements from the stump of the neck to the proximal edge of the lesser sigmoid notch of the ulna. All the measurements were performed three times by three observers acting independently.

The results were highly reproducible with intra- and interclass correlations of > 0.99. The mean difference between the measurement on the excised head and the distance from the stump of the neck and the lesser sigmoid notch was −0.02 mm (−1.24 to +0.97). This difference was not statistically significant (p = 0.78).

The proximal edge of the lesser sigmoid notch provides a reliable landmark for positioning a replacement of the radial head and may have clinical application.

Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel.

We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet-rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains.

Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet-rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion.

One of the most controversial issues in total knee replacement is whether or not to resurface the patella. In order to determine the effects of different designs of femoral component on the conformity of the patellofemoral joint, five different knee prostheses were investigated. These were Low Contact Stress, the Miller-Galante II, the NexGen, the Porous-Coated Anatomic, and the Total Condylar prostheses. Three-dimensional models of the prostheses and a native patella were developed and assessed by computer. The conformity of the curvature of the five different prosthetic femoral components to their corresponding patellar implants and to the native patella at different angles of flexion was assessed by measuring the angles of intersection of tangential lines.

The Total Condylar prosthesis had the lowest conformity with the native patella (mean 8.58°; 0.14° to 29.9°) and with its own patellar component (mean 11.36°; 0.55° to 39.19°). In the other four prostheses, the conformity was better (mean 2.25°; 0.02° to 10.52°) when articulated with the corresponding patellar component. The Porous-Coated Anatomic femoral component showed better conformity (mean 6.51°; 0.07° to 9.89°) than the Miller-Galante II prosthesis (mean 11.20°; 5.80° to 16.72°) when tested with the native patella. Although the Nexgen prosthesis had less conformity with the native patella at a low angle of flexion, this improved at mid (mean 3.57°; 1.40° to 4.56°) or high angles of flexion (mean 4.54°; 0.91° to 9.39°), respectively. The Low Contact Stress femoral component had the best conformity with the native patella (mean 2.39°; 0.04° to 4.56°). There was no significant difference (p > 0.208) between the conformity when tested with the native patella or its own patellar component at any angle of flexion.

The geometry of the anterior flange of a femoral component affects the conformity of the patellofemoral joint when articulating with the native patella. A more anatomical design of femoral component is preferable if the surgeon decides not to resurface the patella at the time of operation.

We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly.

External fixation of distal tibial fractures is often associated with delayed union. We have investigated whether union can be enhanced by using recombinant bone morphogenetic protein-7 (rhBMP-7).

Osteoinduction with rhBMP-7 and bovine collagen was used in 20 patients with distal tibial fractures which had been treated by external fixation (BMP group). Healing of the fracture was compared with that of 20 matched patients in whom treatment was similar except that rhBMP-7 was not used.

Significantly more fractures had healed by 16 (p = 0.039) and 20 weeks (p = 0.022) in the BMP group compared with the matched group. The mean time to union (p = 0.002), the duration of absence from work (p = 0.018) and the time for which external fixation was required (p = 0.037) were significantly shorter in the BMP group than in the matched group. Secondary intervention due to delayed healing was required in two patients in the BMP group and seven in the matched group.

RhBMP-7 can enhance the union of distal tibial fractures treated by external fixation.

We performed a biomechanical study to compare the augmentation of isolated fractured vertebral bodies using two different bone tamps. Compression fractures were created in 21 vertebral bodies harvested from red deer after determining their initial strength and stiffness, which was then assessed after standardised bipedicular vertebral augmentation using a balloon or an expandable polymer bone tamp.

The median strength and stiffness of the balloon bone tamp group was 6.71 kN (sd 2.71) and 1.885 kN/mm (sd 0.340), respectively, versus 7.36 kN (sd 3.43) and 1.882 kN/mm (sd 0.868) in the polymer bone tamp group. The strength and stiffness tended to be greater in the polymer bone tamp group than in the balloon bone tamp group, but this difference was not statistically significant (strength p > 0.8, and stiffness p = 0.4).

There are many methods for analysing wear volume in failed polyethylene acetabular components. We compared a radiological technique with three recognised ex vivo methods of measurement.

We tested 18 ultra-high-molecular-weight polyethylene acetabular components revised for wear and aseptic loosening, of which 13 had pre-revision radiographs, from which the wear volume was calculated based upon the linear wear. We used a shadowgraph technique on silicone casts of all of the retrievals and a coordinate measuring method on the components directly. For these techniques, the wear vector was calculated for each component and the wear volume extrapolated using mathematical equations. The volumetric wear was also measured directly using a fluid-displacement method. The results of each technique were compared.

The series had high wear volumes (mean 1385 mm³; 730 to 1850) and high wear rates (mean 205 mm³/year; 92 to 363). There were wide variations in the measurements of wear volume between the radiological and the other techniques. Radiograph-derived wear volume correlated poorly with that of the fluid-displacement method, co-ordinate measuring method and shadowgraph methods, becoming less accurate as the wear increased. The mean overestimation in radiological wear volume was 47.7% of the fluid-displacement method wear volume.

Fluid-displacement method, coordinate measuring method and shadowgraph determinations of wear volume were all better than that of the radiograph-derived linear measurements since they took into account the direction of wear. However, only radiological techniques can be used in vivo and remain useful for monitoring linear wear in the clinical setting.

Interpretation of radiological measurements of acetabular wear must be done judiciously in the clinical setting. In vitro laboratory techniques, in particular the fluid-displacement method, remain the most accurate and reliable methods of assessing the wear of acetabular polyethylene.

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group.

Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p < 0.05).

Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.

Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules (ProOsteon) would improve the incorporation of bone and implant fixation. We also compared the response to using ProOsteon alone against bone allograft used in isolation. We implanted two non-weight-bearing hydroxyapatite-coated implants into each proximal humerus of six dogs, with each implant surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1.

After three weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own.

ProOsteon alone cannot be recommended as a substitute for allograft around non-cemented implants, but should be used to extend the volume of the graft, preferably with the addition of a growth factor.

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells.

Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.

Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1⁺) and stem cell factor receptor, CD117 (c-kit⁺) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1⁺ mononuclear cell (MNC^sca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC^{sca-1+,c-kit+} counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.

Sca-1⁺ mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.

Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.