Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.
Distal radius fractures (DRFs) are one of the most common types of fracture and one which is often treated surgically. Standard X-rays are obtained for DRFs, and in most cases that have an intra-articular component, a routine CT is also performed. However, it is estimated that CT is only required in 20% of cases and therefore routine CT's results in the overutilisation of resources burdening radiology and emergency departments. In this study, we explore the feasibility of using deep learning to differentiate intra- and extra-articular DRFs automatically and help streamline which fractures require a CT. Retrospectively x-ray images were retrieved from 615 DRF patients who were treated with an ORIF at the Royal Brisbane and Women's Hospital. The images were classified into AO Type A, B or C fractures by three training registrars supervised by a consultant. Deep learning was utilised in a two-stage process: 1) localise and focus the region of interest around the wrist using the YOLOv5 object detection network and 2) classify the fracture using a EfficientNet-B3 network to differentiate intra- and extra-articular fractures. The distal radius region of interest (ROI) detection stage using the ensemble model of YOLO networks detected all ROIs on the test set with no false positives. The average intersection over union between the YOLO detections and the ROI ground truth was The proposed DRF classification framework using ensemble models of YOLO and EfficientNet achieved satisfactory performance in intra- and extra-articular fracture classification. This work demonstrates the potential in automatic fracture characterization using deep learning and can serve to streamline decision making for axial imaging helping to reduce unnecessary CT scans.
Intramedullary nailing is the standard fixation method for displaced diaphyseal fractures of the tibia in adults. Anecdotal clinical evidence indicates that current nail designs do not fit optimally for Asian patients. This study aimed to develop a method to quantitatively assess the fitting of two nail designs for Asian tibiae. We used 3D models of two different tibial nail designs (ETN (Expert Tibia Nail) and ETN-Proximal-Bend, Synthes), and 20 CT-based 3D cortex models of Japanese cadaver tibiae. The nail models were positioned inside the medullary cavity of the intact bone models. The anatomical fitting between nail and bone was assessed by the extent of the nail protrusion from the medullary cavity into the cortical bone, which in a real bone would lead to axial malalignments of the main fragments. The fitting was quantified in terms of the total surface area, and the maximal distance of nail protrusion. In all 20 bone models, the total area of the nail protruding from the medullary cavity was smaller for the ETN-Proximal-Bend (average 540 mm2) compared to the ETN (average 1044 mm2). Also, the maximal distance of the nail protruding from the medullary cavity was smaller for the ETN-Proximal-Bend (average 1.2 mm) compared to the ETN (average 2.7 mm). The differences were statistically significant (p < 0.05) for both the total surface area and the maximal distance measurements. For all bone models, the nail protrusion occurred on the posterior side in the middle third of the tibia. For 12 bones the protrusion was slightly lateral to the centre of the shaft, for seven bones it was centred, and for one bone it was medial to the shaft. The ETN-Proximal-Bend shows a statistical significantly better intramedullary fit with less cortical protrusion than the original ETN. The expected clinical implications of an improved anatomical nail fit are fewer complications with malreduction and malalignments, a lower likelihood for fracture extension and/or new fracture creation during the nail insertion as well as an easier handling for the nail insertion. By utilising computer graphical methods we were able to conduct a quantitative fit assessment between implanted nail and bone geometry in 3D. In addition to the application in implant design, the developed method could potentially be suitable for pre-operative planning enabling the surgeon to choose the most appropriate nail design.
To elucidate the molecular biology of fracture healing, murine models are preferred. We performed a study with the first internal fixation system that allows studying murine fracture healing in a controlled mechanical environment, to characterise the timing of the fracture healing cascade with this model, based on a histological evaluation. Femoral osteotomies were performed in 68 male C57BL/six mice and stabilised with locking internal fixation plates in either stiff, or defined, flexible configurations. Healing progression was studied at 10 time points between 3 and 42 days post- surgery. After surgery, mice were radiographed to confirm the correct implant positioning. After sacrifice, the extracted femora were processed for decalcified histology. Thin sections were taken as serial transverse sections and stained for subsequent histomorphometric analysis and three-dimensional reconstruction of the different fracture callus tissues. The surgery was successful in 62 animals. Only six6 (8.8%) animals had to be sacrificed due to complications during surgery. The post-operative radiographs demonstrated a high reproducibility of implant positioning and no implant failure or screw loosening occurred during the experimental period. The improved consistency in surgical technique leading to more uniform results represents a key advantage of this system over other mouse fracture healing models. As such, it may allow a reduction in the sample size needed in future murine fracture healing studies. The histological evaluation confirmed the lack of a periosteal callus, and exclusively endosteal, intramembraneous bone formation in the bones stabilised with the stiff implants. The bones that were stabilised with the more flexible internal fixation plates showed additional endochondral ossification with extensive, highly asymmetrical, periosteal callus formation. Our results demonstrate that this murine fracture model leads to different healing patterns depending on the flexibility of the chosen plate system. This allows researchers to investigate the molecular biology of fracture healing in different ossification modes by selection of the appropriate fixation.
Queensland is in the phase to develop a comprehensive, integrated state wide Trauma System with support from the Queensland Health and Emergency Services. A strategic step in this circumstance is benchmarking the current trauma system with other established trauma systems, to compare performance and indicators of trauma care. Queensland’s first recognized Adult Major Trauma Service, the Princess Alexandra Hospital (PAH) in Brisbane, was compared with the results of the established Trauma Registry of the German Trauma Society (DGU). This study analysed the whole range of trauma care, from the scene of the accident to discharge from the hospital.
This benchmarking study helps to reflect the current trauma care coming to PA Hospital, even many issues remain unanswered in a retrospective study. This presentation will review the integrated approach of Queensland to streamline the trauma care and highlights the first steps taken to improve the efficiency of the system.
Successful treatment of bone fractures requires a balance between stability, to restore functional anatomy and allow early mobilisation (and thus avoid dystrophy). The healing occurs through complex interactions of inducing, enabling and inhibitory factors. The mechanical environment (e.g. stress and strain) in/around the fracture site regulates tissue changes throughout the healing process, including the formation of a fibro-cartilaginous callus and its progressive replacement by bone. The mechanical and biological environment is controlled substantially by the selection of the fracture stabilisation method achieving either absolute stability (mostly achieved with compression plating technique) or relative stability allowing a limited amount of dynamic fracture displacement across the fracture gap. A number of treatments may be used to accomplish these conditions, ranging from splinting with a plaster cast, external fixator or an intramedullary nail to rigid internal fixation using plates affixed to the bone fragments. Fixation methods are presently selected on the basis of general guidelines, but nevertheless the optimal stability/instability remains unclear and relies heavily on the surgeon’s experience. With the recently more and more widely used locking plates the question of the optimal fixation technique and applied stability to the fracture zone especially in simple fractures have raised again. To fill this knowledge gap, an interdisciplinary approach with in vitro and in vivo experiments seems to be essential. Analysing clinical situations and the healing course with mathematical modelling and computational simulations can further aid to understand the healing conditions in respect to stability. This presentation will give an overview on the role of the mechanical environment in fracture healing, and demonstrating clinical examples that highlight the relevance of this research.
Since the early nineties clinical experience were gained with locking plates to stabilize long bone fractures. Firstly with a Point Contact Fixator, a device making the step from a conventional plate to an internal fixator, than with pure precontured internal fixators for the periaticular regions or nowadays with plates giving the option for the placement of locking or conventional cortical screws and are so called Locked Compression Plate (LCP). Almost every new development for extraarticular fracture stabilization reflects this development. Despite today’s broad, worldwide acceptance of the fixation technique, someone should be very clear about the benefits and the underlying concept to avoid failures, complications and unnecessary costs. Clear clinical benefits have been proven in complex fractures of the metaphysis and joints, furthermore the fixation of highly osteoporotic and/or periprosthetic fractures became more reliable. Also the technique of minimally invasive plating – the so-called biological plating –, where the fracture zone is only bridged and therefore the fracture often is not exposed any more, was facilitated with the new internal fixators. However, the process should not be overused, particularly in cases of insufficient surgical experience, because the technical demanding minimally invasive procedures can have detrimental effects on the fracture alignment and therefore on the later outcome. Not to forget the extended use of intraoperative x-ray exposure to control the reduction and implant fixation. Applying locking plates, the surgeon should never forget that bone healing requires still prerequisites in respect to stability and, of course, of other biological stimuli. This reflects the ongoing discussion, how a simple long bone fracture, should be optimal stabilized with an internal fixator, the amount of bone/implant fixations contacts and the timing for necessary further operations in present of delayed healing. The opportunity to combine both stabilization options – conventional screw and locking screw placement – within one implant needs a clear understanding of the underlying fixation issues and requires a clear teaching concept to avoid unfavorable combination of the different screws. In this lecture a broad, critical overview about the worldwide impact of locking plates in long bone fracture treatment will be given including proven advantages as well as discussing detected disadvantages using literature evidence and clinical examples.
Methods: 24 sheep (Merino wethers, mean age 5.6years, mean weight 39.1kg) underwent the trauma model 2 with a severe soft tissue damage and a multifragmentary, distal femur fracture as well as initial stabilisation with an external fixator. After five days of soft tissue recovery, the animals were definitively operated with an internal fixator (LCP) randomised either by a minimally invasive or open approach. The sheep were sacrificed after 4 and 8 weeks (two groups), mechanical testing performed and statistically analysed with ANOVA test. Results: After 4 weeks, torsional rigidity is significantly higher in the MIPO group (30.1r10.6(SD)%) of fractured to intact bones, p<
0.05) compared to ORIF group (9.8r12.4(SD)%), while ultimate torque also shows increased values for MIPO technique (p=0.11). After 8 weeks, the differences in mechanical properties levelled out, but still higher values for the MIPO group (p=0.36/p=0.26). Conclusion: In the early stage of fracture healing, minimally invasive plate osteosynthesis shows advanced healing pattern compared to open fixation technique. This advantage seems to level out over time.
Volume and density of fracture callus are important outcome parameters in fracture healing studies. These values provide an indication for the recovery of the mechanical function of the bone. Traditionally, fracture callus’ have been evaluated from radiographs, which represent 2D projections of the three-dimensional structures, therefore such an analysis can be affected by many artefacts. With the availability of Computer Tomography (CT) scanners for the evaluation of healing bones, it is now possible to perform precise, three-dimensional reconstructions of the fracture callus and therefore to evaluate true three-dimensional callus volumes and bone mineral densities. We wanted to make use of this technology in the evaluation of a study looking at the healing of a multifragmentary fracture in sheep after 4 and 8 weeks of healing time (Wullschleger et al, ANZORS, 2006). Our goal was to develop a protocol that would allow for the standardised calculation of cortical bone and callus tissue volumes with minimal user influence. Here, we report on the development of this evaluation protocol and some early results. A clinical CT scanner was used to scan the experimental limbs, immediately after the sheep had been euthanized. Further analysis of the CT dataset was accomplished with the commercial computer software Amira. The region of interest was cropped to a 9 cm section of the bone shaft, guaranteed to comprise the entire fracture callus. Next, the cortical bone and the callus tissue were segmented by choosing appropriate threshold values for the measured grey levels. The volume of the segmented regions was then calculated by the software. The application of this protocol to six CT scans from our experimental study resulted in average callus volumes of 12.21 ± 1.96 (standard deviation) cm2 after 4 weeks healing time and 14.28 ± 1.58 cm2 after 8 weeks healing time. In conclusion, we demonstrated the feasibility of using CT data for a quantitative 3D analysis of callus volumes. While this technique is undoubtedly superior to the estimation of callus volumes from two-dimensional radiographs, the absolute accuracy of the results will need to be determined by comparison with histological data.
Regenerative medicine techniques are currently being investigated to replace damaged cartilage. Critical to the success of these techniques is the ability to expand the initial population of cells while minimising de-differentiation to allow for hyaline cartilage to form. Three-dimensional culture systems have been shown to enhance the differentiation of chondrocytes in comparison to two-dimensional culture systems. Additionally, bioreactor expansion on microcarriers can provide mechanical stimulation and reduce the amount of cellular manipulation during expansion. The aim of this study was to characterise the expansion of human chondrocytes on microcarriers and to determine their potential to form cartilaginous tissue in vitro. High-grade human articular cartilage was obtained from leg amputations with ethics approval. Chondrocytes were isolated by collagenase digestion and expanded in either monolayers (104 cells/cm2) or on CultiSpher-G microcarriers (104 cells/mg) for three weeks. Following expansion, monolayer cells were passaged and cells on microcarriers were either left intact or the cells were released with trypsin/EDTA. Pellets from these three groups were formed and cultured for three weeks to establish the chondrogenic differentiation potential of monolayer-expanded and microcarrier-expanded chondrocytes. Cell viability, proliferation, glycosaminoglycan (GAG) accumulation, and collagen synthesis were assessed. Histology and immunohistochemistry were also performed. Human chondrocytes remained viable and expanded on microcarriers 10.2±2.6 fold in three weeks. GAG content significantly increased with time, with the majority of GAG found in the medium. Collagen production per nanogram DNA increased marginally during expansion. Histology revealed that chondrocytes were randomly distributed on microcarrier surfaces yet most pores remained cell free. Critically, human chondrocytes expanded on microcarriers maintained their ability to redifferentiate in pellet culture, as demonstrated by Safranin-O and collagen II staining. These data confirm the feasibility of microcarriers for passage-free cultivation of human articular chondrocytes. However, cell expansion needs to be improved, perhaps through growth factor supplementation, for clinical utility. Recent data indicate that cell-laden microcarriers can be used to seed fresh microcarriers, thereby increasing the expansion factor while minimising enzymatic passage.
With the development and popularisation of minimally invasive surgical methods and implants for fracture fixation, it is increasingly important that available implants are pre-contoured to the specific anatomical location for which they are designed. Due to differences in the bone morphology it is impossible to design single implants that are universally applicable for the entire human population. A recent study on the fit of a distal periarticular medial tibia plate to Japanese bones supported the need for shape optimisation [1]. The present study aimed to quantify and optimise the fit of the same plate for an extended dataset of Japanese tibiae. Forty-five 3D models of the outer bone contour of Japanese tibiae were used. The average age of the specimens was 67 years with an average height of 156 cm. All bone models were considered to be within a normal range without any bony pathology. An anatomical fit of the plate was defined with four criteria [1]. The current plate shape was optimised based on the quantitative results of the plate fitting. Two different optimised plate shapes were generated. The current plate shape achieved an anatomical fit on 13% of tibias from the dataset. Plate 1 achieved an anatomical fit for 42% and Plate 2 a fit for 67% of the bone models. If either Plate 1 or Plate 2 is used, then the anatomical fit can be increased from 13% to 82% for the same dataset. For 12 (27%) of the 45 bones both modified plate shapes were fitting. The results for the fit of the current plate shape are comparable to findings of a similar study on the anatomical fitting of proximal tibia plates [2]. The obtained results indicate that for the available dataset no further modification is warranted for the shaft region of the modified plates. Further optimization of the distal regions of Plate 1 and Plate 2 will be possible. This study shows that in order to achieve an anatomical fit of the plate to the medial Malleolus at least two different plate shapes will be required.
In recent years, plate osteosynthesis in metaphyseal and diaphyseal long bone fractures has been increasingly applied in a minimally invasive fashion. Several clinical studies describe a beneficial effect of the smaller additional soft tissue damage, resulting in satisfying fracture and soft tissue healing. However, is the surgical soft tissue damage really evidently smaller and the recovery faster? A trauma model with severe, circumferential soft tissue damage to the distal right thigh and a distal multifragmentary (AO type C) femur fracture was carried out on 24 male sheep. After five days temporary external fixation, an internal fixator was placed either by a conventional open lateral approach or by minimally invasive technique. To assess the soft tissue damage and its recovery within the first 14 days, local compartment pressure monitoring as well as daily measurements of systemic markers (Creatin Kinase, CK and Lactate Dehydrogenase, LDH) in blood were performed. The local monitoring with a special probe (Neurovent PTO, Raumedic AG, Germany) within the quadriceps muscle allowed the measurement of compartment pressure (CP), as well as temperature. The CK and LDH levels responded to the severe trauma with high peaks within the first 48 hours post trauma. After the internal fixator operations CK levels illustrate a significantly lower increase (p<
0.05) in the minimally invasive group compared to the open approach group in the first two days postoperatively. LDH levels show lower values for the minimally invasive group (p=0.06). The values of CP present an initial increase after the trauma and then higher values (p=0.08) after the open plating operation. For the intracompartmental temperature no statistical differences were found, too (p=0.17). These results, with reduced additional soft tissue damage and faster recovery in the minimally invasive approach group, reflect the clinical experience and expectations. However, while minimally invasive plate osteo-synthesis is certainly a desired option for fracture fixation, good surgical skills are required to insure that the reduced surgical trauma is in line with optimal fracture healing. The influence of the two different approaches on the bone healing per se, as well as the influence on soft tissue functionality, has yet to be demonstrated.
Volume and density of fracture callus are important outcome parameters in fracture healing studies. These values provide an indication for the recovery of the mechanical function of the bone. Traditionally, fracture callus’ have been evaluated from radiographs, which represent 2D projections of the three-dimensional structures; therefore such an analysis can be affected by many artefacts. With the availability of Computer Tomography (CT) scanners for the evaluation of healing bones, it is now possible to perform precise, three-dimensional reconstructions of the fracture callus and therefore to evaluate true three-dimensional callus volumes and bone mineral densities. We wanted to make use of this technology in the evaluation of a study looking at the healing of a multifragmentary fracture in sheep after 4 and 8 weeks of healing time (Wullschleger et al, ANZORS, 2006). Our goal was to develop a protocol that would allow for the standardised calculation of cortical bone and callus tissue volumes with minimal user influence. Here, we report on the development of this evaluation protocol and some early results. A clinical CT scanner was used to scan the experimental limbs, immediately after the sheep had been euthanized. Further analysis of the CT dataset was accomplished with the commercial computer software Amira. The region of interest was cropped to a 9 cm section of the bone shaft, guaranteed to comprise the entire fracture callus. Next, the cortical bone and the callus tissue were segmented by choosing appropriate threshold values for the measured grey levels. The volume of the segmented regions was then calculated by the software. The application of this protocol to six CT scans from our experimental study resulted in average callus volumes of 12.21 ± 1.96 (standard deviation) cm2 after 4 weeks healing time and 14.28 ± 1.58 cm2 after 8 weeks healing time. In conclusion, we demonstrated the feasibility of using CT data for a quantitative 3D analysis of callus volumes. While this technique is undoubtedly superior to the estimation of callus volumes from two-dimensional radiographs, the absolute accuracy of the results will need to be determined by comparison with histological data.