Objectives. Many in vitro studies have investigated the mechanism by which mechanical signals are transduced into biological signals that regulate bone homeostasis via periodontal ligament fibroblasts during orthodontic treatment, but the results have not been systematically reviewed. This review aims to do this, considering the parameters of various in vitro mechanical loading approaches and their effects on osteogenic and osteoclastogenic properties of periodontal ligament fibroblasts. Methods. Specific keywords were used to search electronic databases (EMBASE, PubMed, and Web of Science) for English-language literature published between 1995 and 2017. Results. A total of 26 studies from the 555 articles obtained via the database search were ultimately included, and four main types of biomechanical approach were identified. Compressive force is characterized by static and continuous application, whereas tensile force is mainly cyclic. Only nine studies investigated the mechanisms by which periodontal ligament fibroblasts transduce mechanical stimulus. The studies provided evidence from in vitro mechanical loading regimens that periodontal ligament fibroblasts play a unique and dominant role in the regulation of bone remodelling during orthodontic tooth movement. Conclusion. Evidence from the reviewed studies described the characteristics of periodontal ligament fibroblasts exposed to mechanical force. This is expected to benefit subsequent research into periodontal ligament fibroblasts and to provide indirectly evidence-based insights regarding orthodontic treatment. Further studies should be performed to explore the effects of static tension on cytomechanical properties, better techniques for static compressive force loading, and deeper analysis of underlying regulatory systems. Cite this article: M. Li, C. Zhang, Y. Yang. Effects of mechanical forces on osteogenesis and osteoclastogenesis in human periodontal ligament fibroblasts: A systematic review of in vitro studies. Bone Joint Res 2019;8:19–31. DOI: 10.1302/2046-3758.81.BJR-2018-0060.R1

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

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

Bone is a dynamic tissue that undergoes continuous mechanical forces. Mechanical stimuli applied on scaffolds resembling a part of the human bone tissue affects the osteogenesis [1]. Poly(3,4-ethylenedioxythiophene) (PEDOT) is a piezoelectric material that responds to mechanical stimulation producing an electrical signal, which in turn promotes the osteogenic differentiation of bone-forming cells by opening voltage-gated calcium channels [2]. In this study we examined the biological behavior of pre-osteoblastic cells seeded onto lyophilized piezoelectric PEDOT-containing scaffolds applying uniaxial compression. Two different concentrations of PEDOT (0.10 and 0.15% w/v) were combined with a 5% w/v poly(vinyl alcohol) (PVA) and 5% w/v gelatin, casted into wells, freeze dried and crosslinked with 2% v/v (3-glycidyloxypropyl)trimethoxysilane and 0.025% w/v glutaraldehyde. The scaffolds were physicochemically characterized by FTIR, measurement of the elastic modulus, swelling ratio and degradation rate. The cell-loaded scaffolds were subjected to uniaxial compression with a frequency of 1 Hz and a strain of 10% for 1 h every second day for 21 days. The loading parameters were selected to resemble the in vivo loading situation [3]. Cell viability and morphology on the PEDOT/PVA/gelatin scaffolds was determined. The alkaline phosphatase (ALP) activity, the collagen and calcium production were determined. The elastic modulus of PEDOT/PVA/gelatin scaffolds ranged between 1 and 5 MPa. The degradation rate indicates a mass loss of 15% after 21 days. The cell viability assessment displays excellent biocompatibility, while SEM images display well-spread cells. The ALP activity at days 3, 7 and 18 as well as the calcium production are higher in the dynamic culture compared to the static one. Moreover, energy dispersive spectroscopy analysis revealed the presence of calcium phosphate in the extracellular matrix after 14 days. The results demonstrate that PEDOT/PVA/gelatin scaffolds promote the adhesion, proliferation, and osteogenic differentiation of pre-osteoblastic cells under mechanical stimulation, thus favoring bone regeneration

Intraosseous Transcutaneous Amputation Prosthesis (ITAP) is a new generation of limb replacements that can provide to amputees, an alternative solution to the main problems caused by the most common used external prosthesis such as pressure sores, infections and unnatural gait. ITAP is designed as one pylon osteointegrated into the bone and protruding through the skin, allowing both the mechanical forces to be directly transferred to the skeleton and the external skin being free from frictions and infections. The skin attachment to the implant is fundamental for the success of the ITAP, as it prevents the implant to move and consequently fail. In this study we wanted to test if cell viability and attachment was improved using TiO2 nanotubes. Human keratinocytes and human dermal fibroblasts were seeded for three days on TiO2 nanotubes with different sizes (18–30nm, 40–60nm and 60–110nm), compared with controls (smooth titanium) and tested for viability and attachment. A Mann-Whitney U test was used to compare groups where p values < 0.05 were considered significant. The results showed that the viability and cell attachment for keratinocytes were significantly higher after three days on controls comparing with all nanotubes (p=0.02), while attachment was higher on bigger nanotubes and controls. Cell viability for fibroblasts was significantly higher on nanotubes between 40 and 110nm comparing with smaller size and controls (p=0.03), while investigation of cell attachment is ongoing. From these early results, we can say that TiO2 nanotubes can improve the soft tissue attachment on ITAP. Further in-vitro and ex-vivo experiments on cell attachment will be carried out

Scoliosis is a disease characterised by vertebral rotation, lateral curvature and changes in sagittal profile. The role of mechanical forces in producing this deformity is not clear. It is thought that abnormal loading deforms the disc, which becomes permanently wedged. Modelling and in vitro studies suggest that such deformations should increase intradiscal pressure. Intradiscal pressure has been measured previously in a variety of clinical environments. The aim of this study is to measure pressure profiles across scoliotic discs to provide further information on the role of mechanical forces in scoliosis. Pressure readings were obtained in consented patients with ethical approval using a needle-mounted sterilised pressure transducer (Gaeltec, Dunvegan, Isle of Skye) calibrated as described previously. The transducer needle was introduced into the disc of an anaesthetised patient during routine anterior scoliosis surgery and pressure profiles measured. Signals were collected, amplified and analysed using Power-lab and a laptop computer. Pressure profiles across 10 human scoliotic discs from 3 patients have been measured to date. Pressures varied from 0.1 to 1.2 MPa. Annular pressures showed high pressure, non-isotropic regions on the concave but not convex side of these discs. Nuclear pressures recorded from the discs of these scoliotic patients were higher than those recorded previously in non-scoliotic recumbent individuals

Background. To investigate the new theory of hydroneurolysis and hydrodissection in the treatment of carpal tunnel syndrome (CTS). Independently of the fluid hydrodissolution works due to mechanical forces and it may have some positive effects in patients with ischemic damage caused by scar tissue pressure at the nerve's surface. Methods. A prospective blind clinical study of 31 patients suffering from carpal tunnel syndrome, established by nerve conduction studies and clinical tests. 14 patients (out of 29), who refused to undergo an open operation as a treatment to their disease at this point of time, were treated with a simple ultrasound-guided injection at the proximal carpal tunnel. In order to exclude the biochemical influence of the fluid in the treating disease we choosed to infiltrate 3 cc. of normal saline 0,9%. In the follow-up period our group was asked to answer to a new Q-DASH score and visual analogue scale (VAS) 100/100 in 2, 4 and 8 weeks. Results. At the end of the second month we found only 2 out of 14 patients of the infiltration's group with clinical improvement. As far as the control group (17 patients), there was just one patient with recovery of the symptoms at the end of the second month who avoided operation. The rest 16 patients experienced insistence or worsening of CTS while they were waiting to be operated (mean time till operation in our department's waiting list: 2 months) and underwent a surgical decompression of the median nerve. Comparing the two groups in Q-DASH score, VAS 100/100 and ultrasound cross sectional area measurements we found no statistical difference between the two groups at the endpoint of our follow-up period. Conclusion. As far as nerve entrapment syndromes we proved that normal saline hydrodissolution appears to be non effective as a conservative treatment. The mechanical way of action seems to have only very short term effects. Level of Evidence. II

We investigated factors that were thought to be associated with an increased incidence of squeaking of ceramic-on-ceramic total hip replacements. Between June 1997 and December 2008 the three senior authors implanted 2406 primary total hip replacements with a ceramic-on-ceramic bearing surface. The mean follow-up was 10.6 years. The diagnosis was primary osteoarthritis in each case, and no patient had undergone previous surgery to the hip. We identified 74 squeaking hips (73 patients) giving an incidence of 3.1% at a mean follow-up of 9.5 years (4.1 to 13.3). Taller, heavier and younger patients were significantly more likely to have hips that squeaked. Squeaking hips had a significantly higher range of post-operative internal (p = 0.001) and external rotation (p = 0.003) compared with silent hips. Patients with squeaking hips had significantly higher activity levels (p = 0.009). A squeaking hip was not associated with a significant difference in patient satisfaction (p = 0.24) or Harris hip score (p = 0.34). Four implant position factors enabled good prediction of squeaking. These were high acetabular component inclination, high femoral offset, lateralisation of the hip centre and either high or low acetabular component anteversion. This is the largest study to date to examine patient factors and implant position factors that predispose to squeaking of a ceramic-on-ceramic hip. The results suggest that factors which increase the mechanical forces across the hip joint and factors which increase the risk of neck-to-rim impingement, and therefore edge-loading, are those that predispose to squeaking

PURPOSE. Recently, in tissue engineering several methods using stem cells have been developed to repair chondral and osteochondral defects. Most of these methods rely on the use of scaffolds. Studies in the literature have demonstrated, first in animals and then in humans, that the use of mesenchymal stem cells withdrawn by several methods from adipose tissue allows to regenerate hyaline articular cartilage. In fact, it has been cleared that adipose-derived cells have multipotentiality equivalent to bone marrow-derived stem cells and that they can very easily and very quickly be isolated in large amounts enabling their immediate use in operating room for one-step cartilage repair techniques. The purpose of this study is to evaluate the therapeutic effect of adipose-derived stem cells on cartilage repair and present our experience in the treatment of knee cartilage defects by the novel AMIC REPAIR TECHNIQUE AUGMENTED by immersing the collagen scaffold with mesenchymal stem cells withdrawn from adipose tissue of the abdomen. MATERIALS AND METHODS. Fat tissue processing involves mechanical forces and does not mandatorily require any enzymatic or chemical treatment in order to obtain the regenerative cells from the lipoaspirate. In our study, mesenchymal adipose stem cells were obtained by non-enzymatic filtration or microfragmentation of lipoaspirates of the abdomen adipose tissue that enabled the separation of the stromal vascular fraction and were used in one-step reconstruction of knee cartilage defects by means of this new AUGMENTED AMIC TECHNIQUE. The focal defects underwent bone marrow stimulation microfractures, followed by coverage with collagen double layer resorbable membrane (Chondro-gide. TM. -Geistlich Pharma AG, Wolhusen, Switzerland) soaked in the cells obtained from fat in 18 patients, aged between 31 and 58 years, at the level of the left knee in 10 cases and in the right in eight, with follow-up ranging between 12 and 36 months. RESULTS: Surgical procedures have been completed without technical problems neither intraoperative or early postoperative complications. The evaluation scores (IKDC, KOOS and VAS) showed a significant improvement, more than 30%, at the initial 6 months follow-up and furtherly improved in the subsequent follow-ups. Also the control MRIs showed a progressive filling and maturation of the repair tissue of the defects. CONCLUSIONS. Since we are reporting a short and medium-term experience, it is not, of course, possible to provide conclusive assessment considerations on this technique, as the experience has to mature along with the progression of follow-ups. The simplicity together with the absence of intraoperative difficulties or immediate complications and the experience gained by other authors, first in animals and then in early clinical cases, makes it, however, possible to say that this can be considered one of the techniques to which resort for one-step treatment of cartilage defects in the knee because it improves patient's conditions and has the potential to regenerate hyaline-like cartilage. Future follow-up works will confirm the results

Ankylosing spondylitis (AS) is a progressive multisystem chronic inflammatory disorder. The hallmark of this pathological process is a progressive fusion of the zygapophyseal joints and disc spaces of the axial skeleton, leading to a rigid kyphotic deformity and positive sagittal balance. The ankylosed spine is unable to accommodate normal mechanical forces, rendering it brittle and susceptible to injury. Traumatic hyperextension injury of the cervical spine leading to atlantoaxial subluxation (AAS) in AS patients can often be fatal. We report a non-traumatic mechanism of injury in AS progressing to AAS attributable to persistent hyperextension, which resulted in fatal migration of C2 through the foramen magnum. Cite this article: Bone Joint J 2013;95-B:206–9

Aims

To investigate the extent of bone development around the scaffold of custom triflange acetabular components (CTACs) over time.

Rotating Hinge total knee replacement designs are currently more frequently used for revision total knee replacement. As the designs of these implants have improved over time, the threshold for using them has been lowered. Cases of global instability and severe bone loss have not been adequately addressed by the standard use of unlinked constrained designs. Recurrent dislocation and polyethylene post failure due to cold flow and wear make the use of the unlinked designs insufficient to address the mechanical forces developed in a grossly unstable knee. The linked rotating hinge designs have been able to address global ligamentous instability in four planes. Medial-lateral instability is well addressed by these implants. In cases of severe ankylosis with large flexion contractures, it is often necessary to resect the distal femur above the femoral insertions of the medial and lateral collateral ligaments. The absence of the tethering effect of severely contracted collateral ligaments demand the need for linked designs, although there has been reported success with the use of unlinked designs. Rotating hinges are particularly important for use in cases of recurvatum where an extension stop is incorporated in the design. The design permits slight hyperextension which permits application to clinical situations with incompetent quadriceps strength or paralysis. The clinical results are quite acceptable even though most reports present 65–75% success rates. However, it should also be stated that these patient cohorts represent the most severe cases of revision surgery. Current hinged designs should continue to lower the threshold for use

Aims

To systematically evaluate whether bracing can effectively achieve curve regression in patients with adolescent idiopathic scoliosis (AIS), and to identify any predictors of curve regression after bracing.

Aims

This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

Aims

The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry.

Aseptic loosening of the acetabular component continues to be the most common indication for revision of total hip replacements in younger patients. Early in the evolution of the cemented hip, arthroplasty surgeons switched from removal to retention of the acetabular subchondral bone plate, theorising that unfavourable mechanical forces were the cause of loosening at the bone-cement interface. It is now known that the cause of aseptic loosening is probably biological rather than mechanical and removing the subchondral bone plate may enhance biological fixation of cement to bone. With this in mind, perhaps it is time to revive removal of the subchondral bone as a standard part of acetabular preparation

Matrix metalloproteinases (MMPs), responsible for extracellular matrix remodelling and angiogenesis, might play a major role in the response of the growth plate to detrimental loads that lead to overuse injuries in young athletes. In order to test this hypothesis, human growth plate chondrocytes were subjected to mechanical forces equal to either physiological loads, near detrimental or detrimental loads for two hours. In addition, these cells were exposed to physiological loads for up to 24 hours. Changes in the expression of MMPs -2, -3 and -13 were investigated. We found that expression of MMPs in cultured human growth plate chondrocytes increases in a linear manner with increased duration and intensity of loading. We also showed for the first time that physiological loads have the same effect on growth plate chondrocytes over a long period of time as detrimental loads applied for a short period. These findings confirm the involvement of MMPs in overuse injuries in children. We suggest that training programmes for immature athletes should be reconsidered in order to avoid detrimental stresses and over-expression of MMPs in the growth plate, and especially to avoid physiological loads becoming detrimental. Cite this article: Bone Joint J 2013;95-B:568–73

Aims

Surgical reconstruction of deformed Charcot feet carries a high risk of nonunion, metalwork failure, and deformity recurrence. The primary aim of this study was to identify the factors contributing to these complications following hindfoot Charcot reconstructions.

Failure of a TKA is caused many times from the polyethylene debris or the mechanical forces which lead to loosening mostly to tibial component. The mobile meniscal knee prosthesis could provide solution as it simulates better normal knee function. The aim of our study is to present the midterm results of TKA using mobile bearing platform Rotaglide. During the period 2000–2004 we performed 261 TKA with the Rotaglide mobile polyethylene prosthesis (Corin Medical, UK). They are 235 women and 26 men, mean age 76.33 years, and the 93.7% of them (N=245) with primary osteoarthritis. The tibial component was cemented for all them, and for the femur was cementless for 146 cases (hybrid) and cemented for 115. None of them had patella replacement. One hundred five patients (59 hybrid and 46 cemented) were examined clinically and radiologically and the minimum follow-up time was 5 years (mean 6,6 /range 5–8 years). We use the Knee injury and Osteoarthritis Outcome Score (KOOS- range of scale for each subscore 0–100). There was significant improvement of knee function and the majority of our patients were satisfied from the result. Specifically, the score for general symptoms and joint stiffness was 89.1, for pain was 83.3, for daily activities was 75.6 and for the quality of life was 72.5. One patient had revision TKA for femur component aseptic loosening. Our results indicate that the Rotaglide total knee arthroplasty is a great choice for primary knee OA with excellent functional result