Cells typically respond to a variety of geometrical cues in their environment, ranging from nanoscale surface topography to mesoscale surface curvature. The ability to control cellular organisation and fate by engineering the shape of the extracellular milieu offers exciting opportunities within tissue engineering. Despite great progress, however, many questions regarding geometry-driven tissue growth remain unanswered. Here, we combine mathematical surface design, high-resolution microfabrication, in vitro cell culture, and image-based characterization to study spatiotemporal cell patterning and bone tissue formation in geometrically complex environments. Using concepts from differential geometry, we rationally designed a library of complex mesostructured substrates (10. 1. -10. 3. µm). These substrates were accurately fabricated using a combination of two-photon polymerisation and replica moulding, followed by surface functionalisation. Subsequently, different cell types (preosteoblasts, fibroblasts, mesenchymal stromal cells) were cultured on the substrates for varying times and under varying osteogenic conditions. Using imaging-based methods, such as fluorescent confocal microscopy and second harmonic generation imaging, as well as quantitative image processing, we were able to study early-stage spatiotemporal cell patterning and late-stage extracellular matrix organisation. Our results demonstrate clear geometry-dependent cell patterning, with cells generally avoiding convex regions in favour of concave domains. Moreover, the formation of multicellular bridges and collective curvature-dependent cell orientation could be observed. At longer time points, we found clear and robust geometry-driven orientation of the collagenous extracellular matrix, which became apparent with second harmonic generation imaging after ∼2 weeks of culture. Our results highlight a key role for geometry as a cue to guide spatiotemporal cell and tissue organisation, which is relevant for scaffold design in tissue engineering applications. Our ongoing work aims at understanding the underlying principles of geometry-driven tissue growth, with a focus on the interactions between substrate geometry and mechanical forces

Anterior vertebral body tethering (AVBT) is a growth modulating procedure used to manage idiopathic scoliosis by applying a flexible tether to the convex surface of the spine in skeletally immature patients. The purpose of this study is to determine the preliminary clinical outcomes for an adolescent patient cohort. 18 patients with scoliosis were selected using a narrow selection criteria to undergo AVBT. Of this cohort, 11 had reached a minimum follow up of 2 years, 4 had reached 18 months, and 3 had reached 6 months. These patients all demonstrated a primary thoracic deformity that was too severe for bracing, were skeletally immature, and were analysed in this preliminary study of coronal plane deformity correction. Using open-source image analysis software (ImageJ, NIH) PA radiographs taken pre-operatively and at regular follow-up visits post-operatively were used to measure the coronal plane deformity of the major and compensatory curves. Pre-operatively, the mean age was 12.0 years (S.D. 10.7 – 13.3), mean Sanders score 2.6 (S.D. 1.8-3.4), all Risser 0 and pre-menarchal, with mean main thoracic Cobb angle of 52° (S.D. 44.2-59.8°). Post-operatively the mean angle decreased to 26.4° (S.D. 18.4-32°) at 1 week, 30.4° (S.D. 21.3-39.6°) at 2 months, 25.7° (S.D. 18.7-32.8°) at 6 months, 27.9° (S.D. 16.2-39.6°) at 12 months, and 36.8° (S.D. 22.6– 51.0°) at 18 months and 38.2° (S.D. 27.6-48.7°) at 2 years. The change in curve at 2 years post-operative was statistically significant (P=0.004). There were 4 tether breakages identified that did not require return to theatre as yet, one patient underwent a posterior spinal instrumented fusion due to curve progression. AVBT is a promising new growth modulation technique for skeletally immature patients with progressive idiopathic scoliosis. This study has demonstrated a reduction in scoliosis severity

Summary Statement. Patients with adolescent idiopathic scoliosis show clear signs of abnormal motor coordination between the long superficial paraspinal muscles and the deep rotators. These findings suggest an abnormal behavior of the deep rotator muscles at the concave side. Introduction. An imbalance between the myoelectric activity of the muscles of the convexity and the concavity has been described in patients with adolescent idiopathic scoliosis (AIS). These findings are based on EMG patterns recorded with surface electrodes that do not distinguish between deep and superficial muscles. This work was aimed at analyzing the coupled behavior of the superficial and deep paraspinal muscles in subjects with AIS at both sides of the curve. Material. A total of 16 females (mean age, 16.2±4.3 years) with AIS between 20 and 35° Cobb (mean, 32.8±11.9°) underwent electromyography of the paraspinal muscles by direct intramuscular disposable concentric electrodes (Dantec DCN. TM. ) of 25mm and 37mm in length, and 0.46 mm. in diameter. A total of 4 electrodes were inserted at the apex on both sides of the curve (2 in deep rotator muscle and 2 in the long paraspinal superficial muscles). Myoelectrical activity was recorded simultaneously in the four muscle groups in different positions: standing, flexion, extension, right and left lateralizations, and rotations toward the side of the concavity and convexity. A 4-channel Keypoint® electromyography device (Medtronic, Denmark) was used. The recorded signals were analyzed in a laptop with Windows. ®. 7 Intel Core i3 64bit with Matlab. ®. R2012a. The following parameters were analyzed: Signal power, Mean and Median frecuency, and the Dimitrov spectral index, a marker of muscle fatigue. In addition, the signal power in each task was normalised by the signal power in standing position. The records were compared with those obtained in 4 healthy subjects, matched in age, without spinal deformity. Results. The signal amplitude in different subjects and tests ranged from tens of microvolts up to two milivolts. Most of the energy of the EMG signal was concentrated below 500 Hz in power spectrum density chart. In standing position, the activity of the deep muscle was greater than that of the long superficial paraspinal muscles, with higher activation in the convex side (63% of cases). Increased activity of the deep muscles as compared to the surperficial layers was also evident during flexion of the spine, with a higher activity of the deep muscles of the concavity. The 4 muscle groups showed low activity during spine extension movements, though the deep rotator activity was always greater than the superficial paraspinal muscles. In rotation exercises, the most active muscles were found the contralateral with a clear inhibition of the deep muscles of the concavity in the rotation to that side. This did not apply for rotation through the convex side. It was also noticeable that in the case of deep muscles, both sides of the spine require high activation when performing left flexion. Conclusions. Patients with AIS show clear signs of abnormal motor coordination between the superficial paraspinal muscles and the deep rotators. These findings do not clearly define whether this mismatch is primary or secondary to the presence of the deformity although they suggest an abnormal behavior of deep rotator muscles that could have etiopathogenic relevance

Introduction. Subchondral insufficiency fracture of the femoral head (SIF) often occurs in osteoporotic elderly patients. Patients usually suffer from acute hip pain without any obvious antecedent trauma. Radiologically, a subchondral fracture is seen mainly in the superolateral portion of the femoral head. The T1-weighted magnetic resonance (MR) images show a low-intensity band in the subchondral area of the femoral head, which tends to be irregular, disconnected, and convex to the articular surface. This low-intensity band in SIF was histologically proven to correspond to the fracture line with associated repair tissue. Some cases of SIF resolve after conservative treatment, while others progress until collapse, thereby requiring surgical treatment. The prognosis of SIF remains unclear. This study investigated the risk factors that influence the prognosis of SIF based on the progression of the collapse. Methods. Between June 2002 and June 2008, seventeen patients diagnosed as SIF were included in this study. Sequential radiographs were evaluated for the presence of progression of the collapse. The clinical profiles, including the age, body mass index (BMI), follow-up period and Singh index were examined. The morphological characteristics of the low intensity band on the T1-weighted magnetic resonance images were also examined, with regard to the band length, band thickness and band length ratio; which is defined as a proportion of the band length to the weight-bearing portion of the femoral head. Results. Radiographically, a progression of the collapse was observed in 8 of 17 (47.1%) patients. The band length in patients with progression of the collapse (mean: 22.6 mm) was significantly larger than that in those without progression of the collapse (mean: 12.3 mm; P < 0.05). The band length ratio in patients with progression of the collapse (mean: 73.3 %) was also significantly higher than that in those without progression of the collapse (mean: 42.3 %; P < 0.01). No significant differences were seen in the other variables (the age, BMI, follow-up period, Singh index, and band thickness). Conclusion. One of the important differential diagnoses in determining SIF may include osteonecrosis. The shape of the low signal intensity band on the T1-weighted MR images is one of the characteristic findings in SIF: namely, it is generally irregular, serpiginous, convex to the articular surface, and often discontinuous. This low-intensity band is generally surrounded by bone marrow edema. Histopathologically the band in SIF represents the fracture line with associated repair tissue. On the other hand, in osteonecrosis, since the low-intensity band represents repair tissue, it is generally smooth and circumscribes all of the necrotic segments. In this study, the prognosis of SIF varied even though all the patients received similar non-operative treatments. If the prognosis for SIF can be predicted at the early stage, it would allow the design of optimal treatments in each patient. In this preliminary investigation, both the band length and band length ratio were demonstrated to be useful when selecting the optimal treatment for SIF

The aim is to report a rare technique for correction of intramedullary nail acute angular deformity. Intramedullary tibial nail fixation of diaphyseal tibial fractures is the gold standard treatment allowing early mobilisation whilst preserving the soft tissues around the fracture site. Most commonly, intramedullary nails fail by metal fatigue secondary to non union, without significant deformity of the metalwork. Plastic deformity of the nail can result following new acute trauma, particularly before bone union has occurred. This is a clinical challenge as a reamed intramedullary nail is designed to achieve three point fixation with close anatomical fit, such that removal of a bent nail is technically difficult and also risks further damage to bone and soft tissues. We report a case of a 20 year old patient treated with intramedullary nail fixation of a diaphyseal right tibial fracture who was subsequently assaulted 4 weeks post operatively. This produced an unacceptable deformation of the nail into 25 degrees valgus and procurvatum. To remove the nail, the authors used a previously reported but rare technique of partial (up to 50%) nail division on the convex surface of the apex using Midas Rex High Speed Drill to weaken the nail then manipulation to correct deformity with minimal stress. The technique produced minimal metal debris and allowed simple exchange nail replacement without further complication. The authors believe this is the first reported use of the technique from the United Kingdom

Summary. The cartilage layer from cam-type femoroacetabular impingement deformities had lower stiffness and increased permeability compared to normal cartilage. This is consistent with osteoarthritis and supports the hypothesis of abnormal contact stresses. Introduction. Femoroacetabular impingement (FAI) has recently been associated with osteoarthritic (OA) degeneration of the hip and may be responsible for up to 90% of adult idiopathic OA cases. FAI results from deformities in the hip joint which may lead to abnormal contact stresses and degeneration. The more common cam-type deformity consists of a convex anterior femoral head-neck junction which impinges the anterosuperior acetabular rim during flexion and internal rotation of the hip. Increased subchondral bone density has been reported in this region which may be a bone remodelling response to increased contact stress. The abnormal contact is expected to cause degeneration of the cartilage layer. The goal of this study was to assess the mechanical properties of cartilage retrieved from the cam deformity and to compare this with normal articular cartilage from the femoral head. It is hypothesised that the cartilage will have a lower elastic modulus and higher permeability than normal cartilage. Patients & Methods. Osteochondral biopsies were retrieved from nine patients undergoing surgical correction of a symptomatic cam deformity as well as 10 fresh cadaveric specimens (10 hips, 6 donors). An indentation stress relaxation test was performed on each specimen to 10% of the estimated cartilage thickness. A needle penetration test was performed to accurately measure the thickness. The equilibrium modulus was calculated per Hayes et al. A specimen-specific axisymmetric finite element model was used in a non-linear optimization to obtain the fibril-reinforced poroelastic properties of the cartilage that best fit the experimental data. The material properties were non-fibrillar modulus (E. s. ), Poisson's ratio (ν. s. ) and permeability (k) and strain-independent and –dependent moduli (E. 0. , E. ε. )[4]. Results. The equilibrium modulus was 0.14 MPa and 0.63 from surgical and cadaver specimens, respectively (p=0.002). Compared to cadaver specimens, E. s. in surgical specimens was 73% lower (p=0.01), ν. s. was 43% lower (p=0.01) and k was an order of magnitude higher (p=0.02). Fibril moduli were not significantly different (p>0.35). Discussion/Conclusions. This study showed decreased elastic modulus and increased permeability in cartilage from cam deformities compared to cadaver controls. These differences are consistent with changes expected in osteoarthritic cartilage degeneration. Fibril moduli were 14% to 57% lower in surgical specimens consistent with fibrillation, however results were not significant due to high variability. Altered cellular activity and proteoglycan depletion has been reported in cartilage of cam deformities, which are similar to changes expected in osteoarthritis. The altered mechanical and biochemical properties of this cartilage therefore support the hypothesis that osteoarthritis is secondary to cam FAI deformities and is a result of abnormal contact stresses between the deformity and acetabular rim

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

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 report a study of the shapes of the tibial and femoral articular surfaces in sagittal, frontal and coronal planes which was performed on cadaver knees using two techniques, MRI and computer interpolation of sections of the articular surfaces acquired by a three-dimensional digitiser. The findings using MRI, confirmed in a previous study by dissection, were the same as those using the digitiser. Thus both methods appear to be valid anatomical tools. The tibial and femoral articular surfaces can be divided into anterior segments, contacting from 0° to 20 ± 10° of flexion, and posterior segments, contacting from 20 ± 10° to 120° of flexion. The medial and lateral compartments are asymmetrical, particularly anteriorly. Posteromedially, the femur is spherical and is located in a conforming, but partly deficient, tibial socket. Posterolaterally, it is circular only in the sagittal section and the tibia is flat centrally, sloping downwards both anteriorly and posteriorly to receive the meniscal horns. Anteromedially, the femur is convex with a sagittal radius larger than that posteriorly, while the tibia is flat sloping upwards and forwards. Anterolaterally, both the femoral and tibial surfaces are largely deficient. These shapes suggest that medially the femur can rotate on the tibia through three axes intersecting in the middle of the femoral sphere, but that the sphere can only translate anteroposteriorly and even then to a limited extent. Laterally, the femur can freely translate anteroposteriorly, but can only rotate around a transverse axis for that part of the arc, i.e., near extension, during which it comes into contact with the tibia through its flattened distal/medial surface as against its spherical posterior surface

Objectives

The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity.

Trochlear dysplasia is an important anatomical abnormality in symptomatic patellar instability. Our study assessed the mismatch between the bony and cartilaginous morphology in patients with a dysplastic trochlea compared with a control group.

MRI scans of 25 knees in 23 patients with trochlear dysplasia and in 11 patients in a randomly selected control group were reviewed retrospectively in order to assess the morphology of the cartilaginous and bony trochlea. Inter- and intra-observer error was assessed.

In the dysplastic group there were 15 women and eight men with a mean age of 20.4 years (14 to 30). The mean bony sulcus angle was 167.9° (141° to 203°), whereas the mean cartilaginous sulcus angle was 186.5° (152° to 214°; p < 0.001). In 74 of 75 axial images (98.7%) the cartilaginous contour was different from the osseous contour on subjective assessment, the cartilage exacerbated the abnormality.

Our study shows that the morphology of the cartilaginous trochlea differs markedly from that of the underlying bony trochlea in patients with trochlear dysplasia. MRI is necessary in order to demonstrate the pathology and to facilitate surgical planning.

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model.

The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count.

Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.

Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification.

Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone.

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°).

There has been only one limited report dating from 1941 using dissection which has described the tibiofemoral joint between 120° and 160° of flexion despite the relevance of this arc to total knee replacement. We now provide a full description having examined one living and eight cadaver knees using MRI, dissection and previously published cryosections in one knee.

In the range of flexion from 120° to 160° the flexion facet centre of the medial femoral condyle moves back 5 mm and rises up on to the posterior horn of the medial meniscus. At 160° the posterior horn is compressed in a synovial recess between the femoral cortex and the tibia. This limits flexion. The lateral femoral condyle also rolls back with the posterior horn of the lateral meniscus moving with the condyle. Both move down over the posterior tibia at 160° of flexion.

Neither the events between 120° and 160° nor the anatomy at 160° could result from a continuation of the kinematics up to 120°. Therefore hyperflexion is a separate arc. The anatomical and functional features of this arc suggest that it would be difficult to design an implant for total knee replacement giving physiological movement from 0° to 160°.