Among the advanced technology developed and tested for orthopaedic surgery, the Rizzoli (IOR) has a long experience on custom-made design and implant of devices for joint and bone replacements. This follows the recent advancements in additive manufacturing, which now allows to obtain products also in metal alloy by deposition of material layer-by-layer according to a digital model. The process starts from medical image, goes through anatomical modelling, prosthesis design, prototyping, and final production in 3D printers and in case post-production. These devices have demonstrated already to be accurate enough to address properly the specific needs and conditions of the patient and of his/her physician. These guarantee also minimum removal of the tissues, partial replacements, no size related issues, minimal invasiveness, limited instrumentation. The thorough preparation of the treatment results also in a considerable shortening of the surgical and of recovery time. The necessary additional efforts and costs of custom-made implants seem to be well balanced by these advantages and savings, which shall include the lower failures and revision surgery rates. This also allows thoughtful optimization of the component-to-bone interfaces, by advanced lattice structures, with topologies mimicking the trabecular bone, possibly to promote osteointegration and to prevent infection. IOR's experience comprises all sub-disciplines and anatomical areas, here mentioned in historical order. Originally, several systems of Patient-Specific instrumentation have been exploited in total knee and total ankle replacements. A few massive osteoarticular reconstructions in the shank and foot for severe bone fractures were performed, starting from mirroring the contralateral area. Something very similar was performed also for pelvic surgery in the Oncology department, where massive skeletal reconstructions for bone tumours are necessary. To this aim, in addition to the standard anatomical modelling, prosthesis design, technical/technological refinements, and manufacturing, surgical guides for the correct execution of the osteotomies are also designed and 3D printed. Another original experience is about en-block replacement of vertebral bodies for severe bone loss, in particular for tumours. In this project, technological and biological aspects have also been addressed, to enhance osteointegration and to diminish the risk of infection. In our series there is also a case of successful custom reconstruction of the anterior chest wall. Initial experiences are in progress also for shoulder and elbow surgery, in particular for pre-op planning and surgical guide design in complex re-alignment osteotomies for severe bone deformities. Also in complex flat-foot deformities, in preparation of surgical corrections, 3D digital reconstruction and 3D printing in cheap ABS filaments have been valuable, for indication, planning of surgery and patient communication; with special materials mimicking bone strength, these 3D physical models are precious also for training and preparation of the surgery. In Paediatric surgery severe multi planar & multifocal deformities in children are addressed with personalized pre-op planning and custom cutting-guides for the necessary osteotomies, most of which require custom allografts. A number of complex hip revision surgeries have been performed, where 3D reconstruction for possible final solutions with exact implants on the remaining bone were developed. Elective surgery has been addressed as well, in particular the customization of an original total ankle replacement designed at IOR. Also a novel system with a high-tibial-osteotomy, including a custom cutting jig and the fixation plate was tested. An initial experience for the design and test of custom ankle & foot orthotics is also in progress, starting with 3D surface scanning of the shank and foot including the plantar aspect. Clearly, for achieving these results, multi-disciplinary teams have been formed, including physicians, radiologists, bioengineers and technologists, working together for the same goal.
Degenerative meniscal tears are the most common meniscal lesions, representing huge clinical and socio-economic burdens. Their role in knee osteoarthritis (OA) onset and progression is well established and demonstrated by several retrospective studies. Effective preventive measures and non-surgical treatments for degenerative meniscal lesions are still lacking, also because of the lack of specific and accurate animal models in which test them. Thus, we aim to develop and validate an accurate animal model of meniscus degeneration. Three different surgical techniques to induce medial meniscus degenerative changes in ovine model were performed and compared. A total of 32 sheep (stifle joints) were subjected to either one of the following surgical procedures: a) direct arthroscopic mechanical meniscal injury; b) peripheral devascularization and denervation of medial meniscus; c) full thickness medial femoral condyle cartilage lesion. In all the 3 groups, the contralateral joint served as a control.Introduction
Method
Artificial Intelligence (AI) is becoming more powerful but is barely used to counter the growth in health care burden. AI applications to increase efficiency in orthopedics are rare. We questioned if (1) we could train machine learning (ML) algorithms, based on answers from digitalized history taking questionnaires, to predict treatment of hip osteoartritis (either conservative or surgical); (2) such an algorithm could streamline clinical consultation. Multiple ML models were trained on 600 annotated (80% training, 20% test) digital history taking questionnaires, acquired before consultation. Best performing models, based on balanced accuracy and optimized automated hyperparameter tuning, were build into our daily clinical orthopedic practice. Fifty patients with hip complaints (>45 years) were prospectively predicted and planned (partly blinded, partly unblinded) for consultation with the physician assistant (conservative) or orthopedic surgeon (operative). Tailored patient information based on the prediction was automatically sent to a smartphone app. Level of evidence: IV. Random Forest and BernoulliNB were the most accurate ML models (0.75 balanced accuracy). Treatment prediction was correct in 45 out of 50 consultations (90%), p<0.0001 (sign and binomial test). Specialized consultations where conservatively predicted patients were seen by the physician assistant and surgical patients by the orthopedic surgeon were highly appreciated and effective. Treatment strategy of hip osteoartritis based on answers from digital history taking questionnaires was accurately predicted before patients entered the hospital. This can make outpatient consultation scheduling more efficient and tailor pre-consultation patient education.
Malalignment is often postulated as the main reason for the high failure rate of total ankle replacements (TARs). Only a few studies have been performed to correlate radiographic TAR malalignment to the clinical outcome, but no consistent trends between TAR alignment parameters and the clinical outcome were found. No standard TAR alignment measurement method is present, so reliable comparison between studies is difficult. Standardizing TAR alignment measurements and increasing measurable parameters on radiographs in the clinic might lead to a better insight into the correlation between malalignment and the clinical outcome. This study aims to develop and validate a tool to semi-automatic measure TAR alignment, and to improve alignment measurement on radiographs in the clinic. A tool to semi-automatically measure TAR alignment on anteroposterior and lateral radiographs was developed and used by two observers to measure TAR alignment parameters of ten patients. The Intraclass Coefficient (ICC) was calculated and accuracy was compared to the manual measurement method commonly used in the clinic. The tool showed an accuracy of 76% compared to 71% for the method used during follow-up in the clinic. ICC values were 0.94 (p<0.01) and higher for both inter-and intra-observer reliability. The tool presents an accurate, consistent, and reliable method to measure TAR alignment parameters. Three-dimensional alignment parameters are obtained from two-dimensional radiographs, and as the tool can be applied to any TAR design, it offers a valuable addition in the clinic and for research purposes.
Freehand distal interlocking of intramedullary nails is technical demanding and prone to handling issues. It requires the surgeon to precisely place a screw through the nail under x-ray. If not performed accurately it can be a time consuming and radiation expensive procedure. The aims of this study were to assess construct and face validity of a new training device for distal interlocking of intramedullary nails. 53 participants (29 novices and 24 experts) were included. Construct validity was evaluated by comparing simulator metrics (number of x-rays, nail hole roundness, drill tip position and accuracy of the drilled hole) between experts and novices. Face validity was evaluated by means of a questionnaire concerning training potential and quality of simulated reality using a 7-point Likert scale (range 1-7). Mean realism of the training device was rated 6.3 (range 4-7) and mean training potential as well as need for distal interlocking training was rated 6.5 (range 5-7) with no significant differences between experts and novices, p≥0.236. All participants stated that the simulator is useful for procedural training of distal nail interlocking, 96% would like to have it at their institution and 98% would recommend it to their colleagues. Total number of x-rays were significantly higher for novices (20.9±6.4 vs. 15.5±5.3), p=0.003. Successful task completion (hit the virtual nail hole with the drill) was significantly higher in experts (p=0.04; novices hit: n=12; 44,4%; experts hit: n=19; 83%). The evaluated training device for distal interlocking of intramedullary nails yielded high scores in terms of training capability and realism. Furthermore, construct validity was established as it reliably discriminates between experts and novices. Participants see a high further training potential as the system may be easily adapted to other surgical task requiring screw or pin position with the help of x-rays.
Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip. Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging.Introduction and Objective
Materials and Methods
To investigate the utility of virtual reality (VR) simulators in improving surgical proficiency in Orthopaedic trainees for complex procedures and techniques. Fifteen specialty surgeons attending a London Orthopaedic training course were randomised to either the VR (n = 7) or control group (n = 8). All participants were provided a study pack comprising an application manual and instructional video for the Trochanteric Femoral Nail Advanced (TFNA) procedure. The VR group underwent additional training for TFNA using the DePuy Synthes (Johnson and Johnson) VR simulator. All surgeons were then observed applying the TFNA in a Sawbones model and assessed by a blinded senior consultant using three metrics: time to completion, 22-item procedure checklist and 5-point global assessment scale. Participant demographics for the VR and control groups were similar in context of age (mean [SD]: VR group, 31.0 [2.38] years; control group, 30.6 [2.39] years), gender (VR group, 5 [71%] men; control group, 8 [100%] men) and prior experience with TFNA (had applied TFNA as primary surgeon: VR group, 6 [86%]; control group, 7 [88%]). Although statistical significance was not reached, the VR group, on average, outperformed the control group on all three metrics. They completed the TFNA procedure faster (mean [SD]: 18.2 [2.16] minutes versus 19.78 [1.32] minutes; p<0.189), performed a greater percentage of steps correctly (79% versus 66%; p<0.189) and scored a higher percentage on the global assessment scale (75% versus 65%; p<0.232). VR simulators offer a safe and accessible means for Orthopaedic trainees to prepare for and supplement their theatre-based experience. It is vital, therefore, to review and validate novel simulation-based systems and in turn facilitate their improvement. We intend to increase our sample size and expand this preliminary study through a second upcoming surgical course for Orthopaedic trainees in London.
Prosthetic joint infections represent complications connected to the implantation of biomedical devices, they have high incidence, interfere with osseointegration, and lead to a high societal burden. The microbial biofilm, which is a complex structure of microbial cells firmly attached to a surface, is one of the main issues causing infections. Biofilm- forming bacteria are acquiring more and more resistances to common clinical treatments due to the abuse of antibiotics administration. Therefore, there is increasing need to develop alternative methods exerting antibacterial activities against multidrug-resistant biofilm-forming bacteria. In this context, metal-based coatings with antimicrobial activities have been investigated and are currently used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing their efficacy. Here, we propose the use of antimicrobial silver-based nanostructured thin films to discourage bacterial infections. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture, allow tuning silver release, and avoid delamination. To mitigate interference with osseointegration, here silver composites with bone apatite and hydroxyapatite were explored. The antibacterial efficacy of silver films was tested
Despite overwhelming need, with about 9 million osteoarthritis (OA) sufferers in UK alone, little progress has been made towards pathogenesis-based categorising of patients and subsequent intervention. Experimental studies relied heavily on animal models, which is inefficient and expensive, and has often produced drugs failing in phase I/II clinical trials due to off-target side effects or failure to predict human disease in animal models. This project aims to address this challenge by developing a scalable in vitro human organotypic tissue model. The model can be used to simulate OA processes and ultimately, exploited to seek biomarkers for early diagnosis or screen potential drugs for efficacy. We have previously shown that a stratified 3D-tissue akin of articular cartilage can be generated over a 35-day period using a tissue engineering approach with primary human chondrocyte progenitor cells. The engineered tissue mimics native cartilage both in structural organization and biochemical composition. Here, we explore the influence of the nature and homogeneity of initial cell population on cartilage development and maturation.Abstract
Objectives
Methods
During shoulder arthroplasty the native functionality of the diseased shoulder joint is restored, this functionality is strongly dependent upon the native anatomy of the pre-diseased shoulder joint. Therefore, surgeons often use the healthy contralateral scapula to plan the surgery, however in bilateral diseases such as osteoarthritis this is not always feasible. Virtual reconstructions are then used to reconstruct the pre-diseased anatomy and plan surgery or subject-specific implants. In this project, we develop and validate a statistical shape modeling method to reconstruct the pre-diseased anatomy of eroded scapulae with the aim to investigate the existence of predisposing anatomy for certain shoulder conditions. The training dataset for the statistical shape model consisted of 110 CT images from patients without observable scapulae pathologies as judged by an experienced shoulder surgeon. 3D scapulae models were constructed from the segmented images. An open-source non-rigid B-spline-based registration algorithm was used to obtain point-to-point correspondences between the models. The statistical shape model was then constructed from the dataset using principle component analysis. The cross-validation was performed similarly to the procedure described by Plessers et al. Virtual defects were created on each of the training set models, which closely resemble the morphology of glenoid defects according to the Wallace classification method. The statistical shape model was reconstructed using the leave-one-out method, so the corresponding training set model is no longer incorporated in the shape model. Scapula reconstruction was performed using a Monte Carlo Markov chain algorithm, random walk proposals included both shape and pose parameters, the closest fitting proposal was selected for the virtual reconstruction. Automatic 3D measurements were performed on both the training and reconstructed 3D models, including glenoid version, critical shoulder angle, glenoid offset and glenoid center position. The root-mean-square error between the measurements of the training data and reconstructed models was calculated for the different severities of glenoid defects. For the least severe defect, the mean error on the inclination, version and critical shoulder angle (°) was 2.22 (± 1.60 SD), 2.59 (± 1.86 SD) and 1.92 (± 1.44 SD) respectively. The reconstructed models predicted the native glenoid offset and centre position (mm) an accuracy of 0.87 (± 0.96 SD) and 0.88 (± 0.57 SD) respectively. The overall reconstruction error was 0.71 mm for the reconstructed part. For larger defects each error measurement increased significantly. A virtual reconstruction methodology was developed which can predict glenoid parameters with high accuracy. This tool will be used in the planning of shoulder surgeries and investigation of predisposing scapular morphologies.
Although there are predictive equations that estimate the total fat mass obtained from multiple-site ultrasound (US) measurements, the predictive equation of total fat mass has not been investigated solely from abdominal subcutaneous fat thickness. Therefore, the aims of this study were; (1) to develop regression-based prediction equations based on abdominal subcutaneous fat thickness for predicting fat mass in young- and middle-aged adults, and (2) to investigate the validity of these equations to be developed. The study was approved by the Local Research Ethics Committee (Decision number: GO 19/788). Twenty-seven males (30.3 ± 8.7 years) and eighteen females (32.4 ± 9.5 years) were randomly divided into two groups as the model prediction group (19 males and 12 females) and the validation group (8 males and 6 females). Total body fat mass was determined by dual-energy X-ray absorptiometry (DXA). Abdominal subcutaneous fat thickness was measured by US. The predictive equations for total fat mass from US were determined as fat thickness (in mm) × standing height (in m). Statistical analyses were performed using R version 4.0.0. The association between the total fat mass and the abdominal subcutaneous fat thickness was interpreted using the Pearson test. The linear regression analysis was used to predict equations for total body fat mass from the abdominal subcutaneous fat thickness acquired by US. Then these predictive equations were applied to the validation group. The paired t-test was used to examine the difference between the measured and the predicted fat masses, and Lin's concordance correlation coefficient (CCC) was used as a further measure of agreement.Background
Methods
Accurate orientation of the acetabular component during a total hip replacement is critical for optimising patient function, increasing the longevity of components, and reducing the risk of complications. This study aimed to determine the validity of a novel VR platform (AescularVR) in assessing acetabular component orientation in a simulated model used in surgical training. The AescularVR platform was developed using the HTC Vive® VR system hardware, including wireless trackers attached to the surgical instruments and pelvic sawbone. Following calibration, data on the relative position of both trackers are used to determine the acetabular cup orientation (version and inclination). The acetabular cup was manually implanted across a range of orientations representative of those expected intra-operatively. Simultaneous readings from the Vicon® optical motion capture system were used as the ‘gold standard’ for comparison. Correlation and agreement between these two methods was determined using Bland-Altman plots, Pearson's correlation co-efficient, and linear regression modelling.Abstract
Objectives
Methods
In-vitro testing of knee joints remains vital in the understanding of knee surgery and arthroplasty. However, based on the design philosophy of the original Oxford knee simulator, this in-vitro testing has mainly focused on squatting motion. As the activities of daily living might drastically differ from this type of motion, both from a kinematic and kinetic point of view, a new knee simulator is required that allows studying more random motion patterns. This paper describes a novel knee simulator that overcomes the limitations of traditional Oxford simulators, providing both kinematic and kinetic freedom with respect to the applied boundary conditions. This novel test simulator keeps the hip at a fixed position, only providing a single rotational degree of freedom (DOF) in the sagittal plane. In addition, the ankle holds four DOF, including all rotational DOF and the translation along the medio-lateral axis. Combining these boundary conditions leaves five independent DOF to the knee; the knee flexion angle is actively controlled through the positioning of the ankle joint in the antero-posterior and proximal-distal direction. The specimens' quadriceps muscle is actively controlled, the medial and lateral hamstrings are passively loaded. To validate the performance of this simulator, two fresh frozen specimens have been tested during normal squatting and cycling. Their kinematic patterns have been compared to relevant literature data.Background
Methods
Total ankle replacement (TAR) is the main surgical option in case of severe joint osteoarthritis. The high failure rate of current TAR is often associated to inappropriate prosthetic articulating surfaces designed according to old biomechanical concepts such the fixed axis of rotation, thus resulting in non-physiological joint motion. A recent image-based 3D morphological study of the normal ankle (Siegler et al. 2014) has demonstrated that the ankle joint surfaces can be approximated by a saddle-shaped cone with its apex located laterally (SSCL). We aimed at comparing the kinematic effects of this original solution both with the intact joint and with the traditional prosthetic articulating surfaces via in-silico models and in-vitro measurements. Native 3D morphology of ten normal cadaver ankle specimens was reconstructed via MRI and CT images. Three custom-fit ankle joint models were then developed, according to the most common TAR designs: cylindrical, symmetrically-truncated medial apex cone (as in Inman's pioneering measures), and the novel lateral apex cone, i.e. SSCL. Bone-to-bone motion, surface-to-surface distance maps, and ligament forces and deformations were evaluated via computer simulation. Prototypes of corresponding prosthesis components were designed and manufactured via 3D-printing, both in polymer-like-carbon and in cobalt-chromium-molybdenum powders, for in-vitro tests on the cadaver specimens. A custom testing rig was used for application of external moments to the ankle joint in the three anatomical planes; a motion tracking system with trackers pinned into the bone was used to measure tibial, talar and calcaneal motion (Franci et al. 2009), represented then as tibiotalar, subtalar and ankle complex 3D joint rotations. Each ankle specimen was tested in the intact joint configuration and after replacement of the articulating surfaces according with the three joint models: cylindrical, medial apex cone and SSCL. Results. Small intra-specimen data variability in cycle-to-cycle joint kinematics was found in all cadaver ankles, the maximum standard deviation of all rotation patterns being smaller than 2.0 deg. In-silico ligament strain/stress analysis and in-vitro joint kinematic and load transfer measurements revealed that the novel SSCL surfaces reproduce more natural joint patterns than those with the most common surfaces used in current TAR. TAR based on a saddle-shaped skewed truncated cone with lateral apex is expected to restore more normal joint function. Additional tests are undergoing for further biomechanical validation. The present study has also demonstrated the feasibility and the quality of the full process of custom TAR design and production for any specific subject. This implies a thorough procedure, from medical imaging to the production of artificial surfaces via 3D printing, which is allowing for personalised implants to become the future standard in total joint replacement.
Falls and fall-related injuries can have devastating health consequences and form a growing economic burden for the healthcare system. To identify individuals at risk for preventive measures and therapies, fall risk assessment scores have been developed. However, they are costly in terms of time and effort and rely on the subjective interpretation of a skilled professional making them less suitable for frequent assessment or in a screening situation. Small wearable sensors as activity monitor can objectively provide movement information during daily-life tasks. It is the aim of this study is to evaluate whether the activity parameters from wearable monitors correlate with fall risk scores and may predict conventional assessment scores. Physical activity data were collected from nineteen home-dwelling frail elderly (n=19, female=10; age=81±5.6 years, GFI=5.4±1.9, MMSE=27.4±1.5) during waking hours of 4 consecutive days, wearing a wearable 9-axis activity monitor (56×40×15mm, 25g) on the lateral side of the right thigh. The signal was analysed using self-developed, previously validated algorithms (Matlab) producing the following parameters: time spent walking, step count, sit-stand-transfer counts, mean cadence (steps/min), count of stair uses and intensity counts >1.5G. Conventional fall risk assessment was performed using the Tinetti sore (range: 0–28=best), a widely used tool directly determining the likelihood of falls and the Short Physical Performance Battery (SPPB, range: 0–12=best) which measures lower extremity performance as a validated proxy of fall risk. The anxiety to fall during activities of daily living was assessed using the self-reported Short Falls Efficacy Scale-International (FES-I, range: 7–28=worst). Correlations between activity parameters and conventional scores were tested using Pearson's r. The activity parameters (daily means) for the 19 participants were 70.8min (SD=28.7; min-max= 22.8–126.6) of walking, 4427 steps (SD=2344; min-max= 1391–8269) with a cadence 79.3 steps per minute (SD=17.1; min-max=52.8–103.9) and 33.3 sit-stand transfers (SD=9.7; min-max=8.8–48.0). The average Tinetti score was 21.2 (SD=5.1; min-max=10.0–27.0), with SPPB scoring 7.8 (SD=2.4; min-max=3.0–12.0), and FES-I 4.6 (SD=5.1; min-max=7.0–23.0). Strong (r≥0.6) and significant correlations existed between the walking cadence and the Tinetti (r=.60, p=<.01) and SPPB (r=.71, p=<.01) scores. No other correlations were found between the activity parameters and the Tinetti, SPPB and none with the psychological FES-I questionnaire. Conventional fall risk scores and activity data are comparable to literature values and thus representative of home-dwelling frail elderly including a wide range covered for both dimensions. No quantitative activity measure had a predictive value for fall risk assessment. Strongly correlated with Tinetti and SPPB, objectively measured cadence as a qualitative parameter seems a useful parameter for remotely identifying fall risk in frail elderly. The perceived anxiety to falls was not correlated to quantitative and qualitative activity parameters suggesting that this psychological aspect hardly affects activity. Wearable activity monitors seem a valid tool to assess fall risk remotely and thus allow low cost, frequent and large group screening of frail elderly towards a health economically viable tool for a growing societal need. The predictive quality of activity monitored data may be increased by deriving additional qualitative measures from the activity data.
First works focuses on the characterization (physical and biological) of this biomaterial. Current work had studied osteoinductive and osteoconductive capacity of these hydrogels. Bone is a dynamic and vascularized tissue that has the ability of naturally healing upon damage. Nevertheless, in the case of critical size defects this potential is impaired. Present approaches mainly consider autografts and allografts, which presents several limitations. Bone Tissue Engineering (BTE) is based on the use of 3D matrices to guide both cellular growth, differentiation to promote bone regeneration. Hence, matrices can contain biological materials such as cells and growth factors. Our project aims to design a hydrogel for BTE, particularly for bone lesion filling. We previously showed that a porous 3D hydrogel, Glycosyl-Nucleoside-Fluorinated (GNF) is: 1) non-cytotoxic to clustered human Adipose Mesenchymal Stem Cells (hASCs), 2) bioinjectable and 3) biodegradable. Therefore, this novel class of hydrogels show promise for the development of therapeutic solutions for BTE [1]. The hypothesis of this research was that improving the capacity to promote the adhesion of cells by adding collagen gel matrices and bone morphogenic protein 2 (BMP-2) to improve the bone regenerative potential of this gel. Collagen is a protein matrix well known for its cytocompatibility [2]. BMP-2, have been shown ability to induce bone formation in combination with an adequate matrix [3]. Thereby, the overall aim of this work was to design, develop and validate a new composite hydrogel for BTE. GNF was prepared as previously described in detail[1], at a concentration of 3% (w/v). Type I-collagen gel was prepared from rat-tail tendons at a concentration of 4 g/L [2]. hASCs were isolated from human adipose tissue in our laboratory. To establish a suitable microenvironment for cell proliferation and differentiation cells were seeded in collagen and then GNF gel was added and the resulting mixture was blended, BMP-2 (InductOs ® Kit) is added to this preparation (5µm BMP-2/ml). Fluorometry was used to follow BMP2 release Adding collagen hydrogel improve cell adhesion, survivals and proliferation rather than simple GNF hydrogel. This novel gel composite has the ability to sustain hASCs adhesion and differentiation towards the osteoblastic lineage (positive ALP cells). Fluorometry showed the ability of our hydrogel to prolong the residence of BMP-2 ( Adding collagen to GNF allowed to obtain gels showing satisfactory cell-behaviour. In parallel, the presence of GNF hydrogel helps to improve mechanical properties of the biomaterial (hydrogel stability and controlled release of BMP-2). The first
Cutting rodent's bone ends and irrigation of the medullary canal is the common method used for cells collection in allogenic transplantation, however it does not yield sufficient cells for autologous transplantation. The aim of this experiment was to establish and validate a method for bone marrow collection for autologous MSCs transplantation. Two collection methods were examined: 1) Transection of the bone ends and irrigation of the medullary canal, 2) Trephining of the bone with a hypodermic needle without aspiration. Then cell harvesting was compared in the idealised laboratory situation and under simulated surgery. First, two lower limbs were harvested from the same rat cadaver for comparison, bone marrow in one limb was collected by cutting the femoral head and the distal tibia and irrigation of the canal through drilled holes at the distal end of the femur and proximal end of the tibia. Other limb, hypodermic needle was used as a trephining tool into the medullary canal multiple times without applying negative pressure and rinsed from inside and outside. Second, bone marrow was harvested from another rat's cadaver in the surgery room to simulate the conditions needed for autologous transplantation. The number of cells from irrigation method was 1.28*106 cells, whereas that from trephining method reached 17*106. The number cells from the bone marrow harvested in the surgery room was found 29.6*106. We report a novel technique for harvesting cells for autologous cell therapy from only one limb. A significantly larger number of cells from bone marrow could be collected using the needle trephining method. There is no negative effect on the viability of cells after bone marrow harvesting in the surgery room.
Hydrogels as scaffolds provide a suitable environment for the cells (biocompatibility, biodegradability). Their biomechanical properties are very important to provide not only direct support to the surrounding tissue but also provide a local microenvironment. There is an interest in composite hydrogels with hydroxylapatite or bioactive glass (BAG) for tuning of their bioactivity and biomechanical properties [1]. Hydrogels were prepared from a polysaccharide gellan gum (GG), dissolved in ultrapure water at 90°C under constant stirring to a final concentration of 2 wt.% GG. Sodium-free BAG (70 wt.% SiO2, 30 wt.% CaO) was synthesized using a sol-gel technique with particles of ∼100 nm, clustered to ∼10 µm large agglomerates [1]. The hydrogel composites were prepared by admixing up to 2–8 wt.% of BAG powder into a solution of GG during sonication, and pouring the hot BAG-GG suspension with following cooling to room temperature. Mechanical properties were evaluated using different protocols in creep (0.1 to 1.2 N), strain sweep (1 to 20 µm) and frequency scan (100 to 0.1 Hz) modes, with specimens immersed in water at 25°C. Maximum load (or deformation) before breaking of scaffold materials is a very important material property but is rarely measured. Here creep experiments at different applied stresses were carried out first. These loads exert more proper stress on the scaffold material that results in deformation, which is not the same as during deformation in relaxation or stress-strain tests [2]. The second set of experiments was made at physiologically relevant conditions (1 Hz frequency and small amplitude-controlled deformation) [3]. Amount of 2% BAG was found to be sufficient to get nearly linear deformation in the whole measured strains region, but at higher concentration stress deviated from linearity at strains exceeding ∼0.5% at 1 Hz. Storage modulus (E') did not significantly change and the loss tangent was found nearly constant (∼0.1) for the whole frequency range, indicating a strong network structure of BAG-doped hydrogel. Additions of 2% BAG give a ten-fold increase in both storage and loss moduli, whereas further increase of BAG content does not show further stiffening. The application of tailored protocols [3] allowed analysis of dynamic, creep and relaxation tests in the same device with same specimens, which might be not possible for other techniques. Creep data would provide valuable information in addition to dynamic modes to predict long-term behaviour of the composite hydrogels. Properly tailored protocols could mimic, for example, articular cartilage or other tissue working conditions and allow evaluation of the side effects like swelling at early stage, which measurements are usually rather cumbersome.
Osteoarthritis is a joint condition affecting an estimated eight million people in the UK. The kinematics of walking and the impact experienced are thought to play an important role in the initiation and progression of the disease. Previous studies have looked the effect of osteoarthritis on the kinematics of walking in a laboratory environment. This work is part of the Newcastle Thousand Families Study which has followed a cohort of 1142 members since birth in 1947. Optoelectronic gait analysis methods are unsuitable for this environment, so inertial measurement units are being used. This study focuses on the validation of a protocol using inertial sensors to assess gait in the clinical environment. The sensors measure orientation in three dimensions. Our hypothesis was that an attachment position that minimises the movement of the sensor relative to the segment during gait was more important than the proximity of the sensor to anatomical landmarks. The effect of sampling rate, fatty tissue movement and material type were also tested Seven sensors (Xsens, Netherlands) were attached to participants on top of the foot, on the tibial plateau, on the lateral surface of the femur 10cm proximal to the lateral epicondyle, and over the sacrum. Attachment is by Velcro straps over the top of clothing for the waist, thigh and shank sensors, and with double-sided hypoallergenic tape on the foot. Four calibration movements are performed followed by a walking trial of ten paces down a corridor at a self-selected speed. Data is recorded wirelessly at a sampling rate of 50Hz. The calibration movements and trials are repeated twice and the time taken is 20 minutes. Measurement of the joint angles in the sagittal plane was used to assess the effect of changing the sensor position, simulating fatty tissue movement, and variation of material type underneath the sensor. The foot and thigh sensors were displaced in the distal direction by up to 10cm, the shank and waist sensors were displaced in the proximal direction by 5cm. Material types of different elasticity were tested. Fatty tissue movement beneath the straps was simulated using hydration gel packs. Each attachment scenario was repeated five times on a single subject. A “normal” attachment scenario was used to establish a baseline for repeatability of hip, knee and ankle angle measurement (mean±standard deviation of 49±1.28°, 61.5±1.28° and 33.5±0.69° respectively). Repeatability is comparable to that reported for an opto-electronic system (45±1.8°, 63±1.9° and 36±1.5°). Displacement of the foot, shank and waist sensors had no effect on the repeatability. Displacement of the thigh sensor decreased the repeatability for the knee and hip joint angles (52±3.22° and 62.5±2.91°). As the thigh sensor moved closer to the knee the movement artefact experienced increased. Altering sampling rate and simulated fatty tissue did not decrease repeatability. Of the materials tested, denim had the greatest affect, decreasing hip and knee angle repeatability (50.0±2.04° and 61.0±1.75°). A sensor attachment position that minimises sensor movement relative to the segment has been shown to produce the greatest repeatability, irrespective of their proximity to bony landmarks. This is particularly true for the femur sensor.
The aim of this study was to validate the use of three models of fracture fixation in the assessment of technical skills. We recruited 21 subjects (six experts, seven intermediates, and eight novices) to perform three procedures: application of a dynamic compression plate on a cadaver porcine model, insertion of an unreamed tibial intramedullary nail, and application of a forearm external fixator, both on synthetic bone models. The primary outcome measures were the Objective Structural Assessment of technical skills global rating scale on video recordings of the procedures which were scored by two independent expert observers, and the hand movements of the surgeons which were analysed using the Imperial College Surgical Assessment Device. The video scores were significantly different for the three groups in all three procedures (p <
0.05), with excellent inter-rater reliability (α = 0.88). The novice and intermediate groups specifically were significantly different in their performance with dynamic compression plate and intramedullary nails (p <
0.05). Movement analysis distinguished between the three groups in the dynamic compression plate model, but a ceiling effect was demonstrated in the intramedullary nail and external fixator procedures, where intermediates and experts performed to comparable standards (p >
0.6). A total of 85% (18 of 21) of the subjects found the dynamic compression model and 57% (12 of 21) found all the models acceptable tools of assessment. This study has validated a low-cost, high-fidelity porcine dynamic compression plate model using video rating scores for skills assessment and movement analysis. It has also demonstrated that Synbone models for the application of and intramedullary nail and an external fixator are less sensitive and should be improved for further assessment of surgical skills in trauma. The availability of valid objective tools of assessment of surgical skills allows further studies into improving methods of training.