We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers. The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface

Little is known about the increase in length of tendons in postnatal life or of their response to limb lengthening procedures. A study was carried out in ten young and nine adult rabbits in which the tibia was lengthened by 20% at two rates 0.8 mm/day and 1.6 mm/day. The tendon of the flexor digitorum longus (FDL) muscle showed a significant increase in length in response to lengthening of the tibia. The young rabbits exhibited a significantly higher increase in length in the FDL tendon compared with the adults. There was no difference in the amount of lengthening of the FDL tendon at the different rates. Of the increase in length which occurred, 77% was in the proximal half of the tendon. This investigation demonstrated that tendons have the ability to lengthen during limb distraction. This occurred to a greater extent in the young who showed a higher proliferative response, suggesting that there may be less need for formal tendon lengthening in young children

We assessed the prevalence of abnormal ankle reflexes in 1074 adult patients attending orthopaedic clinics and related it to age. Those with possible pathological causes of reflex loss were excluded. The absence of one or both reflexes was significantly related to increasing age; all patients under 30 years had both reflexes. Few had absent reflexes between 30 and 40 years, but over 40 years, the proportion with both reflexes absent increased rapidly from 5% (40 to 50 years) to 80% (90 to 100 years). Unilateral absence did not show the same pattern of increase being 3% to 5% at 40 to 60 years and 7% to 10% at over 60 years. Our results suggest that a significant number of ‘normal’ adults have unilateral absence of an ankle reflex, but this finding is rare enough to be a definite clinical sign, irrespective of age

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells. Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation

The human acetabulofemoral joint is commonly modelled as a pure ball-and-socket joint, but there has been no quantitative assessment of this assumption in the literature. Our aim was to test the limits and validity of this hypothesis. We performed experiments on four adult cadavers. Cortical pins, each equipped with a marker cluster, were implanted in the pelvis and the femur. Movements were recorded using stereophotogrammetry while an operator rotated the cadaver’s acetabulofemoral joint, exploiting the widest possible range of movement. The functional consistency of the acetabulofemoral joint as a pure spherical joint was assessed by comparing the magnitude of the translations of the hip joint centre as obtained on cadavers, with the centre of rotation of two metal segments linked through a perfectly spherical hinge. The results showed that the radii of the spheres containing 95% of the positions of the estimated centres of rotation were separated by less than 1 mm for both the acetabulofemoral joint and the mechanical spherical hinge. Therefore, the acetabulofemoral joint can be modelled as a spherical joint within the considered range of movement (flexion/extension 20° to 70°; abduction/adduction 0° to 45°; internal/external rotation 0° to 30°)

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures. A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks. In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect. Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing

When transferring tissue regenerative strategies involving skeletal stem cells to human application, consideration needs to be given to factors that may affect the function of the cells that are transferred. Local anaesthetics are frequently used during surgical procedures, either administered directly into the operative site or infiltrated subcutaneously around the wound. The aim of this study was to investigate the effects of commonly used local anaesthetics on the morphology, function and survival of human adult skeletal stem cells. Cells from three patients who were undergoing elective hip replacement were harvested and incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA assays. Viability and morphology were further characterised using CellTracker Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an alkaline phosphatase assay. An additional group was cultured for a further seven days to allow potential recovery of the cells after removal of the local anaesthetic. A statistically significant and dose dependent reduction in cell viability and number was observed in the cell cultures exposed to all three local anaesthetics at concentrations of 25% and 50%, and this was maintained even following culture for a further seven days. This study indicates that certain local anaesthetic agents in widespread clinical use are deleterious to skeletal progenitor cells when studied in vitro; this might have relevance in clinical applications

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

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue. At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001). The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced

We investigated the rates of expression of bone morphogenetic protein-2 (BMP-2) in 29 adult patients with high-grade malignant fibrous histiocytoma of soft tissue, using the BMP-2-specific monoclonal antibody, AbH3b2/17, and found that they ranged from 1.9% to 78.9%. The survival at five years of the groups expressing high (≥30%) and low (< 30%) levels of BMP-2 was 85.7% and 36.3%, respectively. Multivariable analysis showed that only BMP-2 had prognostic significance for continuous disease-free survival and for overall survival (p < 0.05). Our findings indicate that over-expression of BMP-2 in malignant fibrous histiocytoma of soft tissue is the most reliable prognostic indicator of the parameters assessed

We evaluated the effects of a serum protein coating on prosthetic infection in 29 adult male rabbits divided into three groups: control, albumin-coated and uncoated. We used 34 grit-blasted, commercially pure titanium implants. Eleven were coated with cross-linked albumin. All the implants were exposed to a suspension of Staphylococcus epidermidis before implantation. Our findings showed that albumin-coated implants had a much lower infection rate (27%) than the uncoated implants (62%). This may be a useful method of reducing the infection of prostheses

The effects of extracorporeal shock waves (ESWT) on tendon healing were assessed by observing histological and biomechanical parameters in a rat model of injury to the tendo Achillis. The injury was created by inserting an 18-G needle through tendo Achillis in 48 adult Wistar albino rats. The animals were divided into three groups. The first group received radiation only after the operation. The second received no shock waves and the third had 500 15 KV shocks on the second post-operative day. All the rats were killed on the 21st day after surgery. Histopathological analysis showed an increase in the number of capillaries and less formation of adhesions in the study group compared with the control group (p = 0.03). A significantly greater force was required to rupture the tendon in the study group (p = 0.028). Our findings suggest a basis for clinical trials using ESWT

We evaluated the efficacy and biocompatibility of porous apatite-wollastonite glass ceramic (AW-GC) as an intramedullary plug in total hip replacement (THR) for up to two years in 22 adult beagle dogs. Cylindrical porous AW-GC rods (70% porosity, mean pore size 200 3m) were prepared. Four dogs were killed at 1, 3, 6 and 12 months each and six at 24 months after implantation. Radiological evaluation confirmed the efficacy of porous AW-CG as an intramedullary plug. Histological evaluation showed osteoconduction at one month and resorption of the porous AW-GC, which was replaced by newly-formed bone, at 24 months. Our findings indicate that porous AW-GC can be used clinically as an intramedullary plug in THR

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats. Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group. Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function

Axial forces were measured during limb lengthening in a series of ten patients with varying pathologies in order to assess the mechanical characteristics of the distracted tissues and the levels of axial force to which soft tissues are subjected during leg lengthening. The pattern of force was found to vary according to the underlying pathology. For post-traumatic shortening in adults both the peak and the resting forces rose steadily during lengthening reaching maximum forces of the order of 300 N. Patients with congenitally short limbs developed very high peak forces (in some cases over 1000 N) and also showed large amounts of force relaxation (typically 400 to 500 N). When very high levels of force were recorded, there was a higher complication rate. In particular, there was a high instance of angular deformity. This occurred because the loads encountered resulted in failure of some of the external fixation frames

Damage to articular cartilage is a common injury, for which there is no effective treatment. Our aims were to investigate the temporal sequence of the repair of articular cartilage and to define a critical-size defect. Full-thickness defects were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of the defects was varied in order to determine the effect that the size and depth of the defect had on its healing. The defects were made in the femoral groove of the knee with one defect per knee and eight knees per group. The tissues were fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and the sections stained with Toluidine Blue. These were then examined and evaluated for several parameters including the degree of metachromasia and the amount of subchondral bone which had reformed in the defect. The defects had a characteristic pattern of healing which differed at different days and for different sizes of defect. Specifically, the defects of 1 mm first peaked in terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of 3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1 mm

We used a rabbit model to investigate the mechanism by which the angulation of fractures is corrected in children. We produced a transverse proximal tibial fracture in one leg of 12 eight-week-old New Zealand white rabbits and measured bone alignment and length and the patterns of bone growth and remodelling. The angle between the joint surfaces changed rapidly to correct the alignment of the limb as a result of asymmetrical growth of epiphyseal plates. In an adult with closed plates, the angle between the joint surfaces cannot therefore improve. The angle at the fracture itself showed slow improvement because of bone drift and the asymmetrical growth of the epiphyseal plates. Remodelling corrected the shape of the bone in the region of the fracture. Periosteal division on the convex side increased the growth of the epiphyseal plate on that side, thus slowing the correction. The effect was relatively small, providing an indication that factors other than the periosteum are important in inducing correction. External torsional deformities developed because of helical growth at the plate. This was probably caused by abnormal posture which induced a torque at the growth plate. Helical growth is the mechanism by which rotational deformities can occur and correct

Limited success in regenerating large bone defects has been achieved by bridging them with osteoconductive materials. These substitutes lack the osteogenic and osteoinductive properties of bone autograft. A direct approach would be to stimulate osteogenesis in these biomaterials by the addition of fresh bone-marrow cells (BMC). We therefore created osteoperiosteal gaps 2 cm wide in the ulna of adult rabbits and either bridged them with coral alone (CC), coral supplemented with BMC, or left them empty. Coral was chosen as a scaffold because of its good biocompatibility and resorbability. In osteoperiosteal gaps bridged with coral only, the coral was invaded chiefly by fibrous tissue. It was insufficient to produce union after two months. In defects filled with coral and BMC an increase in osteogenesis was observed and the bone surface area was significantly higher compared with defects filled with coral alone. Bony union occurred in six out of six defects filled with coral and BMC after two months. An increase in the resorption of coral was also observed, suggesting that resorbing cells or their progenitors were present in bone marrow and survived the grafting procedure. Our findings have shown that supplementation of coral with BMC increased both the resorption of material and osteogenesis in defects of a clinical significance

We have used an experimental model employing the bent tail of rats to investigate the effects of mechanical forces on bones and joints. Mechanical strain could be applied to the bones and joints of the tail without direct surgical exposure or the application of pins and wires. The intervertebral disc showed stretched annular lamellae on the convex side, while the annulus fibrosus on the concave side was pinched between the inner corners of the vertebral epiphysis. In young rats with an active growth plate, a transverse fissure appeared at the level of the hypertrophic cell layer or the primary metaphyseal trabecular zone. Metaphyseal and epiphyseal trabeculae on the compressed side were thicker and more dense than those of the distracted part of the vertebra. In growing animals, morphometric analysis of hemiepiphyseal and hemimetaphyseal areas, and the corresponding trabecular bone density, showed significant differences between the compressed and distracted sides. No differences were observed in adult rats. We found no significant differences in osteoclast number between compressed and distracted sides in either age group. Our results provide quantitative evidence of the working of ‘Wolff’s law’. The differences in trabecular density are examples of remodelling by osteoclasts and osteoblasts; our finding of no significant difference in osteoclast numbers between the hemiepiphyses in the experimental and control groups suggests that the response of living bone to altered strain is mediated by osteoblasts

We examined the roles of methylmethacrylate (MMA) monomer and cementing technique in the formation, and haemodynamic outcome, of pulmonary fat emboli. The preparation of the femoral canal and the cementing technique were studied in four groups of adult dogs as follows: control (no preparation); lavage; cement pressurisation; and cement pressurisation after lavage. We measured the intramedullary pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure and bilateral femoral vein levels of triglyceride, cholesterol and MMA monomer at rest and after reaming, lavage, and cementing. Femoral vein triglyceride and cholesterol levels did not vary significantly from resting levels despite significant elevations in intramedullary pressure with reaming, lavage and cementing (p = 0.001). PAP was seen to rise significantly with reaming (p = 0.0038), lavage (p = 0.0031), cementing (p = 0.0024) and cementing after lavage (p = 0.0028) while the pulmonary capillary wedge pressure remained unchanged. MMA monomer was detected in femoral vein samples when cement pressurisation was used. Intramedullary lavage before cementing had no significant effect on the MMA level. Haemodynamic evidence of pulmonary embolism was noted with reaming and intramedullary canal preparation, irrespective of the presence of MMA monomer. We found no relationship between MMA monomer level and intramedullary pressure, PAP or pulmonary capillary wedge pressure. Our findings suggest that the presence of MMA monomer in femoral venous blood has no effect on the formation of fat emboli or their pulmonary haemodynamic outcome during cemented hip arthroplasty