Abstract. 1.0 Objectives. Predictive structural models resulting in a trabecular bone topology closely resembling real bone would be a step toward 3D printing of sympathetic prosthetics. This study modifies an established trabecular bone structural adaptation approach, with the objective of achieving an improved adapted topology, specifically connectivity, compared to CT imaging studies; whilst retaining continuum level mechanical properties consistent with those reported in experimental studies. Strain driven structural adaptation models successfully identify trabecular trajectories, although tend to overpredict connectivity and skew trabecular radii distribution towards the smallest radius included in the adaptation. Radius adaptation of each trabecula is driven by a mechanostat approach with a target strain (1250 µɛ) below which radius is decreased (resorption), and above which radius is increased (apposition). Simulations include a lazy zone, in which neither resorption nor apposition takes place (1000 to 1500 µɛ); and a dead zone (<250 µɛ) in which complete resorption of trabeculae with the smallest included radius takes place. This study assesses the impact of increasing the dead zone threshold from <250 µɛ to <1000 µɛ, the lower limit of the lazy zone. 2.0 Methods. In-silico structural models with an initial connectivity (number of trabeculae connecting at each joint) of 14 were generated using a nearest neighbour approach applied to a random cloud of points. Trabeculae were modelled using circular beams whose radii were adapted in response to normal strains caused by the axial force and bending moments due to a vertical pressure of 1 MPa applied to the top of the lattice, with the bottom of the lattice fixed in the vertical direction. Lattices in which nodes are either able (rigid jointed) or unable (pin jointed) to transmit bending moments were considered. Five virtual samples of each lattice type were used, and each simulation repeated twice: with a dead zone of either <250 µɛ or <1000 µɛ. 3.0 Results. In pin jointed lattices the increase in dead zone threshold resulted in reduction of predicted Young's Modulus from 580 MPa (95% CI [577 MPa, 583 MPa]) to 408 MPa (95% CI [397 MPa, 419 MPa]) whilst in rigid jointed lattices it increased form 839MPa (95% CI [832 MPa, 846 MPa]) to 933 MPa (95% CI [931 MPa, 936 MPa]). Mean connectivity decreased from 10.2 to 5.8 in pin jointed simulations and from 9.6 to 3.8 in fixed joined simulations. Topological studies of trabecular bone CT images report a mean connectivity of around 3.4. Pin jointed lattice mean radius increased from 33mm to 45mm, and rigid jointed lattice mean radius increased from 33mm to 64mm. Prevalence of smallest included radius beams decreased in both. 4.0 Conclusion. Improved in-silico representations of trabecular bone can be achieved in structural adaptions by increasing the dead zone threshold and adopting a bending dominated (rigid jointed) lattice structure. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

The purpose of this investigation was to evaluate systematically the literature concerning biopsy, MRI signal to noise quotient (SNQ) and clinical outcomes in graft-maturity assessment after autograft anterior cruciate ligament reconstruction (ACLR) and their possible relationships. Methods: The systematic review was reported and conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies through May 2019 evaluating methods of intra-articular ACL autograft maturity assessment were considered for inclusion. Eligible methods were histologic studies of biopsy specimens and conventional MRI studies reporting serial SNQ and/ or correlation with clinical parameters. Ten biopsy studies and 13 imaging studies, with a total of 706 patients, met the inclusion criteria. Biopsy studies show that graft remodeling undergoes an early healing phase, a phase of remodeling or proliferation and a ligamentization phase as an ongoing process even 1 year after surgery. Imaging studies showed an initial increase in SNQ, peaking at approximately 6 months, followed by a gradual decrease over time. There is no evident correlation between graft SNQ and knee stability outcome scores at the short- and long-term follow-up after ACLR. The remodeling of the graft is an ongoing process even 1 year after ACLR, based on human biopsy studies. MRI SNQ peaked at approximately 6 months, followed by a gradual decrease over time. Heterogeneity of the MRI methods and technical restrictions used in the current literature limit prediction of graft maturity and clinical and functional outcome measures by means of MRI graft SNQ after ACLR

Patients with advanced cancer can develop bone metastases in the femur which are often painful and increase the risk of pathological fracture. Accurate segmentation of bone metastases is, amongst others, important to improve patient-specific computer models which calculate fracture risk, and for radiotherapy planning to determine exact radiation fields. Deep learning algorithms have shown to be promising to improve segmentation accuracy for metastatic lesions, but require reliable segmentations as training input. The aim of this study was to investigate the inter- and intra-operator reliability of manual segmentation of femoral metastatic lesions and to define a set of lesions which can serve as a training dataset for deep learning algorithms. F. CT-scans of 60 advanced cancer patients with a femur affected with bone metastases (20 osteolytic, 20 osteoblastic and 20 mixed) were used in this study. Two operators were trained by an experienced radiologist and then segmented the metastatic lesions in all femurs twice with a four-week time interval. 3D and 2D Dice coefficients (DCs) were calculated to quantify the inter- and intra-operator reliability of the segmentations. We defined a DC>0.7 as good reliability, in line with a statistical image segmentation study. Mean first and second inter-operator 3D-DCs were 0.54 (±0.28) and 0.50 (±0.32), respectively. Mean intra-operator I and II 3D-DCs were 0.56 (±0.28) and 0.71 (±0.23), respectively. Larger lesions (>60 cm. 3. ) scored higher DCs in comparison with smaller lesions. This study reveals that manual segmentation of metastatic lesions is challenging and that the current manual segmentation approach resulted in dissatisfying outcomes, particularly for lesions with small volumes. However, segmentation of larger lesions resulted in a good inter- and intra-operator reliability. In addition, we were able to select 521 slices with good segmentation reliability that can be used to create a training dataset for deep learning algorithms. By using deep learning algorithms, we aim for more accurate automated lesion segmentations which might be used in computer modelling and radiotherapy planning

Summary Statement. The purpose of this experimental imaging study is to determine the Poisson's ratio of ovine periosteum, using strain mapping data from an imaging study designed to elucidate the mechanical environment of periosteal progenitor cells in situ during stance shift loading. Introduction. Periosteum is a composite, so-called “smart” or stimuli responsive material that provides a niche for pluripotent cells that exhibit mechanosensitivity in their proliferative and differentiation behavior. The overarching aim of this research program is to explore, understand, and exploit the mechanical signals that promote cell lineage commitment and de novo bone generation during embryonic development and postnatal healing. Further, our working hypothesis is that periosteum derived progenitor cells are highly sensitive to their local mechanical milieu, which guides their proliferation, motility and differentiation behavior. As a first step toward understand the role of periosteum anisotropy on defining the local mechanical milieu of a given progenitor cell, the objective of the current study is to determine the Poisson's ratio of ovine periosteum and its sensitivity to near, mid- and long-range strains. Methods. The Poisson's ratio for the ovine periosteum was determined using strain mapping data from an high resolution imaging study designed to elucidate the mechanical environment of periosteal progenitor cells in situ. The Poisson's ratio of long bone periosteum is given by the relative ratio of strain in the transverse direction to strain in the axial or longitudinal direction. Given high resolution video imaging data, digital image correlation is used to calculate the average strain and Poisson's ratio between three closest neighbors (nearest neighbor), between 25 points in a 50–150 pixel distance (short range, SR), and between 25 points in a 200–400 pixel distance (long range, LR) of the periosteum during an ex vivo loading setup designed to mimic stance shift loading. Results. Short and long range strains vary with spatial location and time during a given gait cycle. Calculations based on nearest neighbor, SR and LR show maximum strain at different time points in the gait cycle, different ranges of strains, as well as a non-uniform strain field that exhibits both spatial and temporal variation. Hence, the Poisson's ratio is highly dependent on location and time. Follow on studies at lower length scales allowing for subcellular length scale strain measurement are underway to accurately account for the in situ mechanical environment of a given periosteal progenitor cell, e.g. in order to relate its functional loading environment to its biological (proliferation, migration, and differentiation) behavior. Discussion/Conclusion. These results underscore the imperative not only to carry out high resolution imaging measurements but also to elucidate the structure-function relationships at smaller length scales, as these are necessary to elucidate both the origins of emergent, advanced material properties of the periosteum as well as mechanically modulation of progenitor cell proliferation, migration and differentiation

Introduction. We investigated whether grey scale early ultrasonography could be used for the accurate initial diagnosis of non displaced occult scaphoid fractures. Methods. This is a prospective blind clinical study that includes 36 patients that came to the emergency room with suspected clinical symptoms for scaphoid fracture but negative initial X-ray's. After that, a high resolution ultrasonography (without Doppler) was performed. Both wrists of each patient were examined, for comparison. After 14 days, new X-rays were performed, which compared to the early sonographic results of the patients. Results. 25 out of the 36 patients that were included in the study found with subperiosteal hematoma, while 11 of them had also cortical discontinuity. Besides, follow-up X-rays were diagnostic of fracture in 22 patients. 7 patients were ultrasound-positive for fracture but their late X-ray's remained negative, while 4 patients were ultrasound-negative with positive X-ray's. We performed a CT scan on these 11 patients, where we found early ultrasound's sensitivity: 87.5%, specificity: 75%, positive prognostic value: 84% and negative prognostic value: 72%. On the other hand, late X-ray's had sensitivity: 87.5%, specificity: 91%, positive prognostic value: 95% and negative prognostic value: 78% in the detection of occult fractures. Conclusion. The use of early scaphoid ultrasound in the E.R. is valuable in the hands of the orthopaedic surgeon and decongests the radiology department and the national health system from further specific and expensive imaging studies. So, this examination offers the possibility to reduce the time of diagnosis of these occult fractures, so as to provide early and correct treatment. Level of Evidence. II

High resolution imaging techniques such as atomic force microscopy, provide a platform to study the fibrillary architecture of biological tissues, but are not capable of imaging the internal microstructure of tissues in 3D. Conversely, multiphoton microscopes facilitate 3D imaging to study the spatial relationship of micro-components within tissues, but without the resolution of atomic force microscopy. The lamina splendens is the most superficial layer of articular cartilage. It is believed to play a crucial role in the health of the tissue. However, the precise form of this layer is uncertain as it has never been independently studied. Here, we use multiphoton microscopy and atomic force microscopy to demonstrate the anatomic form of the lamina splendens. The lamina splendens were peeled from the femoral condyles of healthy, adult sheep (n=20). Using atomic force microscopy, we show that the collagen and elastin form an interweaving fibrillary network at the surface of the lamina splendens and at the interface of the lamina splendens with the underlying cartilage. Moreover, using fluorescent stains; sulforhodamine B and acridine orange, multiphoton microscopy shows the heterogeneous distribution of collagen, elastin and chondrocytes throughout the depth of the lamina splendens. Our results demonstrate the fibrillary and component level architecture of the lamina splendens. We believe our findings provide the backbone of knowledge to advance tissue engineering techniques that will lead to more promising strategies to treat cartilage pathologies, including osteoarthritis. Furthermore, our results provide a starting point to determine the role of the lamina splendens in cartilage pathology

A tendon is a fibrous connective tissue that acts to transmit tensile forces between muscles and bones. It mainly consists of soluble substance, collagen and small volume of elastic fibres, which are produced by tenoblasts and tenocytes. The Achilles tendon is the thickest tendon in the human body that subjects to some of the highest tensile force, thus disorders and ruptures commonly happen. As the insoluble fibrous components in Achilles tendons, the collagen fibrils and elastic fibres have unique spatial structure that plays important functional roles. Despite this, the understanding of relationship between them is still limited due to the lack of imaging evidence. Using confocal and second harmonic generation microscopy, this study aims to comprehensively investigate the spatial relationship of collagen, elastic fibres and tenocytes in hydrated tendons. Longitudinal sections of 50 µm thick and transverse sections of 20 µm thick were cryo-sectioned respectively from the mid-portion of ten rabbit Achilles tendons. Sections were stained with 0.03g/L Acridine Orange (AO) and 1mg/ml Sulforhodamine B (SRB) solution respectively for labelling the nucleus and elastic fibres. The Leica TCS SP2 multiphoton microscopy containing second harmonic generation microscopy can image collagen without labelling. The sections were scanned by the multiphoton microscopy, and images were processed and reconstructed into 3D images to study the spatial structure of collagen, elastic fibres and cells in Achilles tendons. A rabbit Achilles tendon consists of three sub-tendons named flexor digitorum superficialis tendon, medial gastrocnemius tendon and lateral gastrocnemius tendon. Loose connective tissue connects the three sub-tendons and ensures efficient sliding between sub-tendons. The 3D network shows that the mid-portion of Achilles tendons is composed of longitudinal collagen and elastic fibres, while spindle tenocytes rest along the collagen and elastic fibres. Tenocytes appear to have a closer microstructural relationship with the elastic fibres. In comparison with the collagen, tenocytes and elastic fibres only occupy a very small volume in the 3D network. The elastic fibres exist in both tendon proper and endotenons. The tendon sheath and loose connective tissue have a higher cell density, and the cells are large and round while compared with tenocytes. As a component of the extracellular matrix (ECM) in Achilles tendons that closely mediates with the tenocytes, the elastin may participate in the force transition and interaction between tenocytes and the ECM. The elastic fibres may also endow Achilles tendons with unique mechanical properties to stand for tensile force

The posterolateral approach to ankle joint is well suited for ORIF of posterior malleolar fractures. There are no major neurovascular structures endangering this approach other than the sural nerve. The sural nerve is often used as an autologous peripheral nerve graft and provides sensation to the lateral aspect of the foot. Hence every attempt must be made to protect the sural nerve. The aim of this paper is to measure the precise distance of the sural nerve from surrounding soft tissue structures. This is a retrospective image review study including patients with MRI of their ankle from January 09 - Nov 2010. We indentified 78 MRI scans out of which 64 were deemed eligible for assessment. All measurements were made from Axial T1 slices. Measurements were made from the lateral aspect of the TA to the central of the sural nerve, central of sural nerve to the posterior aspect of the peronei muscles and central of the sural nerve to the posterior aspect of fibula. Data were collected on a Microsoft Excel spreadsheet and the descriptive statistics calculated. The key findings of the paper is the safety window for the sural nerve from the lateral border of TA is 7mm, 1.3cm and 2cm at 3 cm above ankle joint, at the ankle joint and at the distal tip of fibula respectively. Similarly the safety window for the nerve from the posterior aspect of fibula is 2cm, 1.6cm, 1.6cm at 3cm above ankle, at the ankle joint and the distal tip of fibula respectively. Our study demonstrates the close relationship of the nerve in relation to tendoachilles, peronei and fibula in terms of exact measurements. The safety margins established in this study should enable the surgeon in preventing endangerment of the sural nerve encountered in this approach

In a study combining tissue mechanics and fracture morphology for the first time, we examined the ruptured surfaces of anterior cruciate ligaments of rabbits and related their appearance to the initial loading conditions. Sixteen specimens were stretched to failure at rates of displacement of 10 and 500 mm/min. We used video images to study the changes which occurred during the fracture process and SEM to examine the appearance of the ruptured surfaces. The surfaces of ligaments tested at 10 mm/min had more pulled-out collagen fibres and the fibres had more pronounced waviness compared with those tested at 500 mm/min. We have shown that the macroscopic appearance of ruptured ligaments can be related to their microscopic appearance and that it is possible to deduce whether failure was by gradual tearing of the fibres or catastrophic failure

Objectives

Acetabular component orientation in total hip arthroplasty (THA) influences results. Intra-operatively, the natural arthritic acetabulum is often used as a reference to position the acetabular component. Detailed information regarding its orientation is therefore essential. The aim of this study was to identify the acetabular inclination and anteversion in arthritic hips.

Objectives

An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia.

Objectives

We aimed to examine the characteristics of deep venous flow in the leg in a cast and the effects of a wearable neuromuscular stimulator (geko; FirstKind Ltd) and also to explore the participants’ tolerance of the stimulator.

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.

We compared time-dependent changes in the biomechanical properties of single-and double-row repair of a simulated acute tear of the rotator cuff in rabbits to determine the effect of the fixation techniques on the healing process.

A tear of the supraspinatus tendon was created in 80 rabbits which were separated into two equal groups. A single-row repair with two suture anchors was conducted in group 1 and a double-row repair with four suture anchors in group 2. A total of ten intact contralateral shoulder joints was used as a control group. Biomechanical testing was performed immediately post-operatively and at four and eight weeks, and histological analysis at four and eight weeks.

The mean load to failure in group 2 animals was greater than in group 1, but both groups remained lower than the control group at all intervals. Histological analysis showed similar healing properties at four and eight weeks in both groups, but a significantly larger number of healed tendon-bone interfaces were identified in group 2 than in group 1 at eight weeks (p < 0.012).

The ultimate load to failure increased with the number of suture anchors used immediately post-operatively, and at four and eight weeks. The increased load to failure at eight weeks seemed to be related to the increase in the surface area of healed tendon-to-bone in the double-row repair group.