Introduction. The reduction of intraoperative blood loss during total knee arthroplasty (TKA) and total hip arthroplasty (THA) and even organ resection is an important factor for surgeons as well as the patient. In order to cauterize blood vessels to stop bleeding diathermy is commonly used and involves the use of high frequency and induces localized tissue damage and burning. Saline-coupled bipolar sealing RFE technology however has been shown to reduce tissue carbonization, however the dosage effects of RFE are not well known for both bone and soft tissue. This study examined sealing progression of blood vessels using a range of energy levels of saline-coupled bipolar RFE on bone and various soft tissues in a non-survival animal study. Materials and Methods. Following institutional ethical approval, three mature sheep were used to examine the cancellous bone of the femoral trochlear groove and soft tissue (liver, kidney, lung, pancreas and mesentry peritoneum) subjected to the following treatment regime varying by watts and time: (1) untreated control, (2) 50 W for 1 sec, 2 sec, 3 sec and 5 sec, (3) 140 W for 1 sec, 2 sec, 3 sec and 5 sec and (4) 170 W for 1 sec, 2 sec, 3 sec and 5 sec. The Aquamantys™ System Generator and hand piece (Salient Surgical Technologies, Inc, Portsmouth, NH) coupled to a saline (0.9% NaCl) drip was used to apply RFE to the various tissues. Two clinical diathermy settings were used as controls. Tissues were immediately harvested, fixed in 10% buffered formalin and prepared for routine paraffin histology. Stained sections were evaluated in a blinded fashion for the acute in vivo response. Result. Soft tissue histology treated with the Aquamantys System revealed varying degrees of coagulation and blood vessel sealing. Initial observations were indicative of hemostasis. Once RFE and saline were applied to the tissues, the blood vessels constricted and platelets were observed along the blood vessels to provide a seal to cover the break in the vessel wall. No smoke or char formation was evident when this system was placed in contact with the tissues. Higher frequency revealed an increased cluster of platelets along the vessel wall. Saline-coupled bipolar RFE application on bone demonstrated blood vessel sealing and clumping of bone marrow. With increased frequency and time red blood cells clumped together however the most significant observation was that the surrounding bone remained normal and no damage was evident. Diathermy however demonstrated a complete disruption of the collagen fibres. Conclusions. Saline-coupled bipolar RFE can provide many clinical benefits not just during orthopaedic reconstruction but also during spine surgery and clinical oncology. The use of high frequencies for longer periods of time enables complete sealing of blood vessels without damage to the tissue or bone

INTRODUCTION. Stimulation of angiogenesis via the delivery of growth factors (GFs) like vascular endothelial growth factor (VEGF) is a promising strategy for the treatment of avascular necrosis (AVN). Tyraminated poly-vinyl-alcohol hydrogels (PVA-Tyr), which have the ability to covalently incorporate GFs, were proposed as a platform for the controlled delivery of therapeutic levels VEGF to the necrotic areas[1]. Nevertheless, PVA hydrophilicity and bioinertness limits its integration with the host tissues. The aim of this study was to investigated the effectiveness of incorporating gelatin, an FDA-approved, non-immunogeneic biomaterial with biological recognition sites, as a strategy to facilitate blood vessels invasion of PVA-Tyr hydrogels and to restore the vascular supply to necrotic tissues. METHODS. Progressively higher gelatin concentrations (0.01–5wt%) were incorporated in the PVA-Tyr network. Hydrogel physico-chemical properties and endothelial cell attachment were evaluated. Afterwards, the capability of the released VEGF and gelatin to promote vascularization was evaluated via chorioallantoic membrane (CAM) assay. VEGF-loaded PVA-Tyr hydrogels with or without gelatin (n=7) were implanted in a subcutaneous mouse model for 3 weeks. Vascularization (CD31+ cells) and cell infiltration (H&E) were evaluated. Finally, AVN was induced in 6 weeks old male piglets as previously described [2]. A transphyseal hole (3mm) was drilled and PVA-Tyr hydrogels with 1% gelatin were delivered in the defects. Piglets were euthanized after 4 weeks and microCT analysis was performed. RESULTS. The incorporation of 1% gelatin significantly enhanced cell attachment without compromising hydrogels physical properties, degradation time, VEGF retention and release. Thus, this gelatin concentration was selected for further analysis. Additionally, the covalent incorporation of VEGF or gelatin to the PVA-Tyr network does not hamper their bioactivity, as both still promoted neo-angiogenesis in a CAM assay. Following subcutaneous implantation, the presence of gelatin did not increase the cellular infiltration in the PVA-Tyr hydrogels. Nevertheless, higher vascular infiltration was observed in the groups where either gelatin or VEGF were included. Additionally, preliminary microCT results indicated that the delivery of PVA-Tyr hydrogels containing 1% gelatin in an AVN model was effective in preventing the necrosis-associated resorption of the bone. DISCUSSION & CONCLUSIONS. These results indicated that the presence of either gelatin or VEGF was sufficient to promote vascular infiltration. Additionally, preliminary results suggested the suitability of the developed hydrogels to treat AVN

Introduction. Osteoarthritis (OA) has historically been thought of as a degenerative joint disease, but inflammation and angiogenesis are increasingly being recognised as contributing to the pathogenesis, symptoms and progression of OA. b-dystroglycan (b-DG) is a pivotal element of the transmembrane adhesion molecule involved in cell-extracellular matrix adhesion and angiogenesis. Matrix metalloproteinases (MMPs) are the main enzymes responsible for cartilage extracellular matrix breakdown and are also implicated in both angiogenesis and b-DG degradation in a number of malignancies. We aimed to investigate the expression and localisation of b-DG and MMP-3, -9, and -13 within cartilage, synovium and synovial fluid and establish their roles in the pathogenesis of OA. Methods. Following ethical committee approval, cartilage, synovium and synovial fluid were obtained from the hip joints of 5 osteoarthritic (patients undergoing total hip replacement) and 5 control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for b-DG expression using Western Blotting and for the distribution of b-DG, MMP-3, -9, and -13 using immunohistochemistry on paraffin embedded tissue. Results. Whilst no significant expression of b-DG was found in cartilage or synovial fluid, b-DG was expressed in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Moreover, b-DG was expressed in endothelium of blood vessels of OA synovium, but not in the normal endothelium. In the endothelium of osteoarthritic synovial blood vessels, b-DG co-localised with MMP -3 and -9. Discussion. Our results demonstrate that b-DG does not act as a cell adhesion molecule binding chondrocytes to the ECM. However, specific immunolocalisation of b-DG within endothelium of inflamed OA blood vessels suggests that b-DG may play a role in angiogenesis associated with OA. Its co-localisation with MMP-3 and -9, previously reported to also have pro-angiogenic roles, may be linked. Further research is required to understand these roles more fully

To evaluate the short-term clinical outcomes of patients treated arthroscopically with chitin-based scaffolding for acetabular chondral defects in conjunction with microfracture compared to microfracture alone. This study is a retrospective analysis of prospectively collected data. A review of charts was performed (2014–2016) on all patients who underwent hip arthroscopy and had microfracture +/− scaffolding for acetabular chondral defects, intraoperative details (lesion size, grade, labral repair/reconstruction) and postoperative complications were recorded with a minimum follow-up of 2 years. Clinical outcomes were assessed by analysing iHOT and HOS scores which were obtained pre-operatively, at six months, one year and two years post-surgery. Plain radiographs were assessed for hip osteoarthritis by Kellgren & Lawrence grading. A total of 60 patients (microfracture=25, scaffolding=35) were included. Patients had a mean age of 36.2 years at the time of the index operation. There were no major adverse events of deep vein 36.2 years at the time of the index operation. There were no major adverse events of deep vein thrombosis, blood vessel or nerve damage, hemarthrosis or device related adverse events in both groups. Two patients were readmitted due to pain as a result of an inflammatory reaction in the scaffolding group. Both treatments of microfracture and scaffolding showed significant improvement in outcome score (iHOT) (p < 0 .001) when compared postoperative to preoperative. Both the arthroscopic treatment of chondral acetabular defects with chitin based scaffolding and microfracture demonstrated significant improvement from their pre-operative outcomes

The Masquelet or induced membrane technique (IMT) is a two-stage surgical procedure used for the treatment of segmental bone defects. In this technique, the defect is first filled with a polymethyl methacrylate (PMMA) spacer, which triggers the formation of a membrane that will encapsulate the defect. During the second surgery, the spacer is carefully removed and replaced by autologous bone graft while preserving the membrane. This membrane is vascularized, contains growth factors, and provides mechanical stability to the graft, all of which are assumed to prevent graft resorption and promote bone healing. The technique is gaining in popularity and several variations have been introduced in the clinical practice. For instance, orthopaedic surgeons now often include antibiotics in the spacer to treat or prevent infection. However, the consequences of this approach on the properties of the induce membrane are not fully understood. Accordingly, in a small animal model, this study aimed to determine the impact on the induced membrane of impregnating spacers with antibiotics frequently used in the IMT. We surgically created a five-mm segmental defect in the right femur of 25 adult male Sprague Dawley rats. The bone was stabilized with a plate and screws before filling the defect with a PMMA spacer. Animals were divided into five equal groups according to the type and dose of antibiotics impregnated in the spacer: A) no antibiotic (control), B) low-dose tobramycin (1.2 g/40 g of PMMA), C) low-dose vancomycin (1 g/40 g of PMMA), D) high-dose tobramycin (3.6 g/40 g of PMMA), E) high-dose vancomycin (3 g/40 g of PMMA). The animals were euthanized three weeks after surgery and the induced membranes were collected and divided for analysis. We assessed the expression of selected genes (Alpl, Ctgf, Runx2, Tgfb1, Vegfa) within the membrane by quantitative real-time PCR. Moreover, frozen sections of the specimens were used to quantify vascularity by immunohistochemistry (CD31 antigen), proliferative cells by immunofluorescence (Ki-67 antigen), and membrane thickness. Microscopic images of the entire tissue sections were taken and analyzed using FIJI software. Finally, we measured the concentration of vascular endothelial growth factor (VEGF) in the membranes by ELISA. No significant difference was found among the groups regarding the expression of genes related to osteogenesis (Alpl, Runx2), angiogenesis (Vegfa), or synthesis of extracellular matrix (Ctgf, Tgfb1) (n = four or five). Similarly, the density of proliferative cells and blood vessels within the membrane, as well as the membrane thickness, did not vary substantially between the control, low-dose, or high-dose antibiotic groups (n = four or five). The concentration of VEGF was also not significantly influenced by the treatment received (n = four or five). The addition of tobramycin or vancomycin to the spacer, at the defined low and high doses, does not significantly alter the bioactive characteristics of the membrane. These results suggest that orthopaedic surgeons could use antibiotic-impregnated spacers for the IMT without compromising the induced membrane and potentially bone healing

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses. Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure. In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future. Cite this article: Bone Joint J 2014;96-B:291–8

It is the prime responsibility of the treating surgeon to identify and treat the vascular injury along with the skeletal trauma. Limbs with combined Orthopaedic and Vascular injuries are traditionally admitted as an Orthopaedic emergency. In a 17 year period we treated 67 cases of vascular injuries (including 16 pseudo aneurysms) associated with fractures and dislocations or soft tissue injuries of the limbs. Three cases have been followed up for over 20 years. All patients were operated by Orthopaedic residents on duty with limited resources, without the help of vascular surgeons. We relied on clinical diagnosis and immediate exploration of the blood vessels rather than time consuming procedure of arteriography. Skeletal stabilisation was achieved by internal or external fixation. Vascular reconstruction involved end to end repair or vein grafting. Fasciotomy was performed in selected cases where the injury-revascularisation time was more than 6 hours. Post-operative care involved limb placement at body level, Sympathetic blockade for 48 hours, vasodilators, Lomodex, Mannitol, Aspirin and antibiotic therapy. Urine was monitored for smoky color indicating myoglobinuria. Though only 17 were repaired within six hours, limb viability with good function was obtained in 51 cases. Complications included 7 deaths, 6 amputations, 2 acute renal failures and delayed occlusion in one case

Introduction. Migration of the trial femoral head is a rarely occurring complication of total hip arthroplasty (THA) performed using the anterolateral approach (ALA). This migration of the trial femoral head under the rectus femoris is extremely risky because of the anatomical situation. Analyzing the morphological character of a case of migration may help us to avoid this risk. Objective. We analyzed the three-dimensional bone morphology using computed tomography (CT) scan images to investigate the physiological characteristics of five migration cases. Methods. We examined 108 patients (21 men, 87 women, 113 hips) who underwent THA via the ALA. The average patient age was 62.9 (range: 30–87) years and average body mass index was 24.4 (range: 18.0–36.0) kg/m2. The exclusion criteria were dysplastic coxarthroses greater than Crowe type II, previous fractures, previous hip operations, and muscle disease. Three-dimensional models of the pelvis and femur were made using ZedHip software® (Lexi, Tokyo, Japan). The anterior superior iliac spine on the affected side (A) and contralateral side (A’), anterior inferior iliac spine (I), and greater trochanter tip (G) were noted in these models. The distances A–I, I–G, and A–G and the angle formed by AA’ and AI were measured (Figure 1, 2). Each hip was classified by the presence (group M) or absence (group N) of migration during surgery. A Fisher's exact probability test, Student's t-test, and Welch's t-test were used to compare the two groups, and p-values less than 0.05 were considered significant. Results. In 5 of the 113 hips, the trial femoral heads migrated under the rectus femoris and were removed safely. No significant differences were found between the gender, height, weight, or BMI of the groups. The average A–I distance was 32.3±3.0 mm (mean±SD) in group M and 39.4±10.4 mm in group N; I–G was 52.2±8.2 mm in group M and 59.7±10.6 mm in group N; and A–G was 64.3±10.3 mm in group M and 76.3±12.3 mm in group N. The average angle formed by AA’ and AI was 50.5±5.8°. Significant differences between the two groups were found for the distances A–I and A–G. Conclusions. In 4.4% of cases, the trial femoral heads migrated under the rectus femoris, which creates a risk for serious complications because major nerve and blood vessels are located nearby. The tendency for migration was expected to be related to the balance between soft tissues. In this study, we found that migration tends to occur in patients with shorter distances between A and I, and A and G. The trial head should be dislocated more carefully in those patients

Chevron osteotomy is a commonly performed procedure for the treatment of hallux valgus and results in AVN of the first metatarsal head in up to 20% of cases. This study aims to map out the arrangement of vascular supply to the first metatarsal head and its relationship to the limbs of the chevron cuts. Ten cadaveric lower limbs were injected with an Indian ink/latex mixture and the feet dissected to evaluate the blood supply to the first metatarsal. The dissection was carried out by tracing the branches of dorsalis pedis and posterior tibial vessels. A distal chevron osteotomy through the neck of the metatarsal was mapped and the relationship of the limbs of the osteotomy to the blood vessels was recorded. The first metatarsal head was found to be supplied by branches from the first dorsal metatarsal, first plantar metatarsal and medial plantar arteries of which the first one was the dominant vessel in 8 of the specimens studied. All the vessels formed a plexus at the plantar-lateral aspect of the metatarsal neck, just proximal to the capsular attachment with varying number of branches from the plexus then entering the metatarsal head. The plantar limb of the proposed chevron cuts exited through this plexus of vessels in all specimens. Contrary to the widely held view, only minor vascular branches could be found entering the dorsal aspect of the neck. The identification of the plantar-lateral corner of the metatarsal neck as the major site of vascular ingress into the first metatarsal head suggests that constructing the chevron osteotomy with a long and thick plantar arm exiting well proximal to the capsular attachment may decrease the incidence of AVN

Haemangiomas are benign tumours with increased number of normal or abnormal appearing blood vessels. They are the commonest soft tissue tumours of infancy and childhood and comprise 7% of all soft tissue tumours. Our study is a retrospective analysis of 120 referred cases of various vascular anomalies in the last 10 years. Eighty cases had confirmed haemangiomas. MRI scan and needle biopsy formed the basis of diagnosis. M:F = 42:38. Mean age at presentation was 34.8 years, with the youngest and eldest patient being 3.5 and 78 years respectively. 5 patients were lost to study. Sites of occurrence were upper limb(32), lower limb(32), axilla(3), foot(5), thumb(1), knee(4), spine(1), posterior chest wall(2). 55/80 patients were managed non-operatively by way of Sclerotherapy/Embolisation, watchful observation or symptomatic treatment. 4/55 cases were assessed to be unsuitable for sclerotherapy and 1 patient was subjected to surgery. 6/55 cases did not respond to sclerotherapy. 25/55 cases were managed with surgical excision. Complete excision was the primary goal of surgery. Intralesional margins were accepted if lesions were close to neurovascular structures. Indications for surgery were 1) Pain with functional and/or developmental disturbance, 2) Sudden increase in size, 3) Recurrent haemarthrosis, 4) Failure of sclerotherapy. There were 3 cases of incomplete excision among those operated. 6/25 cases had recurrence 1-8 years after surgery. Mean follow-up was 38.4 weeks (range6-12 months). We have had a success rate of 81.48% with non-operative management of symptomatic haemangiomas. Surgical excision of haemangiomas has borne 76% satisfactory results for pain relief/functional recovery. We believe that extensive haemangiomata covering large surface areas are not suitable for surgical excision. Majority of cases can be successfully managed non-operatively by way of sclerotherapy/embolisation and watchful observation. MRI scan coupled with trucut needle biopsy has been most successful for diagnosis. Highly vascular sarcomata can mimic haemangiomas, hence histological diagnosis is crucial

To close the surgeon in the control loop is able to take advantages of the fertile sensing information and intelligence from human being so that the complex and unpredictable surgical procedure can be better handled properly. However, there is also weakness to be strengthened. For example, the motion control of the human being is not as accurate as required. Assisted equipment for such purpose may be helpful to the procedure. Exerting large forces during the cutting process may exhaust the operator and cause fatigue. The operator may need power assistance during the surgery procedure. The response speed of human being's may not be adequate to take immediate action in certain critical situations. The constraints from the limbs and human's attention usually cause a significant delay to react the critical situations. This may lead to serious damage by failing to response immediately. For example, in knee replacement procedure, the shape of the knee joint has to be prepared by performing bone resection procedure. The surgeon cuts the bone at certain position and orientation with the help of the cutting jig from the surgical planning. The cutter cut the bone by inserting vibration saw through the slot of the cutting block. The surgeon has to stop the cutter right after the bone has been cut through by the saw so that no surrounding soft tissue, blood vessel, and even important nerves, be damaged. Currently the tactile sensing from the hand is heavily relied on by the surgeon. He has also to be experienced and dexterous. If he fails to draw back the cutter after the bone being cut through, damages to the patient may occur. Therefore there is need to develop a cutting tool, which is intelligent, knows where it is, and is able to judge what the cutting situation is, and further assists the operator to stop the cutter in case that the operator fails to do so, or too slow to response. The benefit to the patient as well as the surgeon will be significant. Therefore the purpose of the paper is to develop an algorithm to implement such functionality of auto-detection of bone cutting through for a bone cutting tool when the cutter has cut through the bone. By the developed method, the intelligent cutter can effectively detect the cutting through condition and then adopt an immediate reaction to prevent the cutter from going further and to avoid unexpected damage. An auto-detection scheme has also been developed for assisting the operator in judging whether the cutter has reached the boundary or not. The auto-detection scheme is based on analyzing the cutting force pattern in conjunction with a bilateral force controller for the hand's on robot. The bilateral force controller consists of two force controllers. The force controller on the master calculates the feedrate of the cutter according to the push force by the operator. Meanwhile, the operator can also feel the cutting force by the force controller on the slave site, which revises the feedrate of the cutter by the measured cutting force. The operator can kinesthetically feel the cutting force from the variation of the feedrate. When the cutter breaks through the boundary of the bone, the cutting force will drop suddenly to almost zero. When this special force pattern occurs, an acknowledge signal of bone been broken through will be activated. The subsequent action will be followed to stop the cutter going further. We implement this concept by defining a “cutting admittance” indicating the resistance encountered by the cutting during bone resection at different cutting feedrate. During the bone resection, the cutting admittance varies from cutting through hard or soft portions of bone. As reaching the cutting boundary, the cutting admittance will suddenly increase. A threshold value will experimentally be determined to indicate cutting through condition. Together with pushing force by the human operator, the criterion for cutting-through detection is defined. Once cutting through is detected, the admittance for cutter movement will be set zero. The cutter stops going further and the operator feel like hitting a virtual wall in front. In this paper we proposed a human robot cooperative operation method by which the robotic system can intelligently detect where the cutter has cut through the bone. Characterisation of bone cutting procedure was performed. This auto detection scheme was developed by analyzing the information of the motion and cutting force information during the bone cutting process, no medical images are required. The auto-detection bone cut through was able to transfer the experiences of human being to quantitative modeling. The developed model has been tested for its applicability and robustness by saw bones and pig's knee joints. Results have shown the virtual wall generated by the real-time bone detection scheme and active constraint control is very accurate and capable of providing a safety enhance module for computer assisted orthopaedic surgery, in particular, in total knee replacement. By this method the robot system can accomplish a safe and accurate bone cutting with a complement of an imageless navigation system and results in a low cost, but safe and effective surgical robot system

Aims

The aticularis genu (AG) is the least substantial and deepest muscle of the anterior compartment of the thigh and of uncertain significance. The aim of the study was to describe the anatomy of AG in cadaveric specimens, to characterize the relevance of AG in pathological distal femur specimens, and to correlate the anatomy and pathology with preoperative magnetic resonance imaging (MRI) of AG.

External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur.

We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment.

Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome.

Cite this article: Bone Joint J 2015;97-B:1296–1300.

We reviewed 234 benign solitary schwannomas treated between 1984 and 2004. The mean age of the patients was 45.2 years (11 to 82). There were 170 tumours (73%) in the upper limb, of which 94 (40%) arose from the brachial plexus or other nerves within the posterior triangle of the neck. Six (2.6%) were located within muscle or bone. Four patients (1.7%) presented with tetraparesis due to an intraspinal extension.

There were 198 primary referrals (19 of whom had a needle biopsy in the referring unit) and in these patients the tumour was excised. After having surgery or an open biopsy at another hospital, a further 36 patients were seen because of increased neurological deficit, pain or incomplete excision. In these, a nerve repair was performed in 18 and treatment for pain or paralysis was offered to another 14.

A tender mass was found in 194 (98%) of the primary referrals. A Tinel-like sign was recorded in 155 (81%). Persistent spontaneous pain occurred in 60 (31%) of the 194 with tender mass, impairment of cutaneous sensibility in 39 (20%), and muscle weakness in 24 (12%).

After apparently adequate excision, two tumours recurred. No case of malignant transformation was seen.

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116