Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution.

β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model.

Applications of weightbearing computed tomography (WBCT) imaging in the foot and ankle have emerged over the past decade. However, the potential diagnostic benefits are scattered across the literature, and a concise overview is currently lacking. Therefore, we aimed to systematically review all reported diagnostic applications per anatomical region in the foot and ankle. A systematic literature search was performed in the electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “weightbearing/standing CT and ankle, hind-, mid- or forefoot”. English language studies analyzing the diagnostic applications of WBCT were included. Studies were excluded if they simulated weightbearing CT, described normal subjects, included cadaveric samples or samples were case reports. The modified Methodological Index for Non-Randomized Studies (MINORS) was applied for quality assessment. The added value was defined as the review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the Prospero database (CRD42019106980). A total of 48 studies (prospective N=8, retrospective N=36, cohort study N=1, diagnostic N=2, prognostic comparative study N=1) were found to be eligible for review. The following diagnostic applications were identified per anatomical area in the foot: ankle (osteoarthritis N=5, ligament injury N=6); hindfoot (deformity N=9); midfoot (Lisfranc injury N=2, flatfoot deformity N=13, osteoarthritis N=1); forefoot (hallux valgus N=12). The identified studies contained diagnostic applications that could not be used on plain radiographs. The mean MINORS equaled 10.1 on a total of 16 (range: 8 to 12). Diagnostic applications of weightbearing CT imaging are most frequently studied in hindfoot deformity, but other area's areas are on the rise. Post-processing of images was identified as the main added value compared to WBRX. However, the findings should be interpreted with caution as the average quality score was moderate. Therefore, future prospective studies are warranted to consolidate the role of WBCT in diagnostic and therapeutic algorithms.

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Knee ligament injury is one of the most frequent sport injuries and ligament reconstruction has been used to restore the structural stability of the joint. Cycling exercises have been shown to be safe for anterior cruciate ligament (ACL) reconstruction and are thus often prescribed in the rehabilitation of patients after ligament reconstruction. However, whether it is safe for posterior cruciate ligament (PCL) reconstruction remains unclear. Considering the structural roles of the PCL, backward cycling may be more suitable for rehabilitation in PCL reconstruction. However, no study has documented the differences in the effects on the knee kinematics between forward and backward pedaling. Therefore, the current study aimed to measure and compare the arthrokinematics of the tibiofemoral joint between forward and backward pedaling using a biplane fluoroscope-to- computed tomography (CT) registration method.

Eight healthy young adults participated in the current study with informed written consent. Each subject performed forward and backward pedaling with an average resistance of 20 Nm, while the motion of the left knee was monitored simultaneously by a biplane fluoroscope (ALLURA XPER FD, Philips) at 30 fps and a 14-camera stereophotogrammetry system (Vicon, OMG, UK) at 120 Hz. Before the motion experiment, the knee was CT and magnetic resonance scanned, which enabled the reconstruction of the bones and articular cartilage. The bone models were registered to the fluoroscopic images using a volumetric model-based fluoroscopy-to-CT registration method, giving the 3-D poses of the bones. The bone poses were then used to calculate the rigid-body kinematics of the joint and the arthrokinematics of the articular cartilage. In this study, the top dead center of the crank was defined as 0° so forward pedaling sequence would begin from 0° to 360°.

Compared with forward pedaling, for crank angles from 0° to 180°, backward pedaling showed significantly more tibial external rotation. Moreover, both the joint center and contact positions in the lateral compartment were more anterior while the contact positions in the medial compartment was more posterior, during backward pedaling. For crank angles from 180° to 360°, the above-observed phenomena were generally reversed, except for the anterior-posterior component of the contact positions in the medial compartment.

Forward and backward pedaling displayed significant differences in the internal/external rotations while the rotations in the sagittal and frontal planes were similar. Compared with forward cycling, the greater tibial external rotation for crank angles from 0° to 180° during backward pedaling appeared to be the main reason for the more anterior contact positions in the lateral compartment and more posterior contact positions in the medial compartment.

Even though knee angular motions during forward and backward pedaling were largely similar in the sagittal and frontal planes, significant differences existed in the other components with different contact patterns. The current results suggest that different pedaling direction may be used in rehabilitation programs for better treatment outcome in future clinical applications.

Summary Statement

A three dimensional meniscal scaffold with controlled fibre diameter and orientation was fabricated by an improved E-Jetting system that mimic the internal structure of natural meniscus. In vitro cellular tests proved its feasibility in meniscal tissue engineering applications.

Patient specific knee modelling has the potential to help understand the development of the mechanically induced degenerative disease, Osteoarthritis. A full joint contact model of the knee involves modelling the bones, ligaments, articular cartilage (AC) and meniscus, as well as, the kinematics and geometry of real joints. These finite element models will inevitably require great computational resource to run and it is desirable to find resource effective material model formulations which can accurately describe the mechanical behaviour of the soft tissues. Biphasic models (BIMs) have long been established as an effective formulation for modelling AC. However, the swelling behaviour caused by changes in the ionic phase is a major recovery mechanism and is neglected in the BIMs. It is therefore believed that BIMs alone are insufficient to fully describe the mechanical behaviour of AC. Instead, a thermal analogy method which is generically a BIM that includes the swelling behaviour has been thought to be suitable and has been validated against literature data using material parameters optimized to match the numerical and experimental results. To ensure the model is suitable for patient specific modelling where it will have the ability to reflect the individual AC material properties of the patients in the mechanical behaviour it predicts, two experiments have been planned and are currently being carried out using bovine AC. The first experiment is to investigate the diffusivity of the tissue in solutions of different molarity by measuring the change in tissue weight over time. Eleven explants are taken from the same bovine articular joint using a 6mm biopsy punch and are left in 10mM of PBS overnight to ensure ionic equilibrium has been reached before experiments are carried out. The explants are then placed in PBS solutions of molarities ranging from 0mM to 10mM and weighed at regular time intervals. In the final stage, the explants are then lyophilized and weighed for determining the volume of water in the tissues. Using Archimedes principle, the change in porosity of the tissue is found. A preliminary study has shown that explants submerged in a solution of 5mM has an approximately 4% change in weight after the first 24h and a further 1.73% change in the following 24h. Control specimens left in a solution of 10mM had a 0% change in weight. The second experiment is to carry out mechanical loading on the AC specimens while submerged in a solution of different ion concentrations. Experiments with various loading conditions are being investigated to explore their efficacy for validation. Preliminary compression tests have been carried out where steps of 1% strain was applied, giving a total of 10% strain. Between each step, strain was held constant until full relaxation has been achieved. The reaction force measured from the second experiment in conjunction with data collected from the first experiment will be compared to results predicted in the numerical model. This will allow the determination of whether thermal analogy is adequate or whether more complex triphasic models need to be considered. Furthermore, the development of these experimental methods will contribute to the validation of other AC material models in the future.

Background

Osteoarthritis (OA), is characterised with a loss of cartilage and pain in affected joints. It is this pain which most patients associate with their condition. Intra-articular (IA) hyaluronan (HA) has been shown to reduce the pain associated with OA both in animal models and in clinical trials. There are purified HA available and in recent years hyaluronan hydrogels, where the material has been cross-linked into networks, have become available. One of these cross-linked HA hydrogels is Durolane¯. This study has sought to evaluate the effect of Durolane in an in vivo model of osteoarthritis.