430 research outputs found
A versatile salt-based method to immobilize glycosaminoglycans and create growth factor gradients
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204547.pdf (Publisher’s version ) (Open Access
Intra-articular drug depots for controlled release of heavy chain only antibodies blocking joint inflammation
No full textFrom intricate to integrated: Biofabrication of articulating joints
No full textArticulating joints owe their function to the specialized architecture and the complex interplay between multiple tissues including cartilage, bone and synovium. Especially the cartilage component has limited self-healing capacity and damage often leads to the onset of osteoarthritis, eventually resulting in failure of the joint as an organ. Although in its infancy, biofabrication has emerged as a promising technology to reproduce the intricate organization of the joint, thus enabling the introduction of novel surgical treatments, regenerative therapies, and new sets of tools to enhance our understanding of joint physiology and pathology. Herein, we address the current challenges to recapitulate the complexity of articulating joints and how biofabrication could overcome them. The combination of multiple materials, biological cues and cells in a layer-by-layer fashion, can assist in reproducing both the zonal organization of cartilage and the gradual transition from resilient cartilage toward the subchondral bone in biofabricated osteochondral grafts. In this way, optimal integration of engineered constructs with the natural surrounding tissues can be obtained. Mechanical characteristics, including the smoothness and low friction that are hallmarks of the articular surface, can be tuned with multi-head or hybrid printers by controlling the spatial patterning of printed structures. Moreover, biofabrication can use digital medical images as blueprints for printing patient-specific implants. Finally, the current rapid advances in biofabrication hold significant potential for developing joint-on-a-chip models for personalized medicine and drug testing or even for the creation of implants that may be used to treat larger parts of the articulating joint. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
On the brink of daily clinical application of objective gait analysis: What evidence do we have so far from studies using an induced lameness model?
No full textQuantitative gait analysis has the potential to offer objective and unbiased gait information that can assist clinical decision-making. In recent years, a growing number of gait analysis systems have come onto the market, highlighting the demand for such technology in equine orthopaedics. However, it is imperative that the measured variables which are used as outcome parameters are supported by scientific evidence and that the interpretation of such measurements is backed by a proper understanding of the biomechanical principles of equine locomotion. This review, which is based on studies on experimentally induced lameness, summarises the currently most widely used methods for gait analysis and the available evidence concerning gait parameters that can be used to quantify gait changes due to lameness. These are discussed regarding their current and future potential for routine clinical application
Near Infrared Spectroscopic Mapping of Functional Properties of Equine Articular Cartilage
No full textMechanical properties of articular cartilage are vital for normal joint function, which can be severely compromised by injuries. Quantitative characterization of cartilage injuries, and evaluation of cartilage stiffness and thickness by means of conventional arthroscopy is poorly reproducible or impossible. In this study, we demonstrate the potential of near infrared (NIR) spectroscopy for predicting and mapping the functional properties of equine articular cartilage at and around lesion sites. Lesion and non-lesion areas of interests (AI, N = 44) of equine joints (N = 5) were divided into grids and NIR spectra were acquired from all grid points (N = 869). Partial least squares (PLS) regression was used to investigate the correlation between the absorbance spectra and thickness, equilibrium modulus, dynamic modulus, and instantaneous modulus at the grid points of 41 AIs. Subsequently, the developed PLS models were validated with spectral data from the grid points of 3 independent AIs. Significant correlations were obtained between spectral data and cartilage thickness (R (2) = 70.3%, p < 0.0001), equilibrium modulus (R (2) = 67.8%, p < 0.0001), dynamic modulus (R (2) = 68.9%, p < 0.0001) and instantaneous modulus (R (2) = 41.8%, p < 0.0001). Relatively low errors were observed in the predicted thickness (5.9%) and instantaneous modulus (9.0%) maps. Thus, if well implemented, NIR spectroscopy could enable arthroscopic evaluation and mapping of cartilage functional properties at and around lesion sites
Musculoskeletal disease in aged horses and its management
No full textMusculoskeletal disorders are the most prevalent health problem in aging horses. They are not life threatening, but are painful and an important welfare issue. Chronic joint disease (osteoarthritis) and chronic laminitis are the most prevalent. Treating osteoarthritis in the elderly horse is similar to treating performance horses, but aims at providing a stable situation with optimal comfort. Immediate medical treatment of flare-ups, long-term pain management, and adaptation of exercise and living conditions are the mainstays of treatment. Laminitis in the geriatric horse is related often to pituitary pars intermedia dysfunction, which may be treated with additional pergolide
How exercise influences equine joint homeostasis
No full textThe maintenance of joint homeostasis is integral to joint health. Knowledge of the influence of exercise on joint homeostasis is not only relevant for determining sustainable levels of equine athletic training, but also for the study of early development of osteoarthritis or cartilage repair in animal models. This review provides an overview of findings derived from in vivo studies and postmortem analyses investigating exercise effects on various joint tissue components in the horse, supplemented where appropriate with data from small animal models. The concept of joint homeostasis and possible methods to quantify this are also discussed, with special attention to the potential benefits and pitfalls of biomarker analysis in synovial fluid. The main conclusion is that biomechanical loading in the form of deliberate exercise has a major influence on the delicate homeostatic balance within the tissues constituting the diarthrodial joint and on their interactions, which is crucial for proper and durable joint function. The amount and intensity of exercise can have a lasting effect on tissue characteristics in juvenile animals, but affects joint homeostasis in mature animals and can affect the delicate balance between physiologic adaptation and development of pathology. Biomarkers in synovial fluid can be helpful in assessing joint homeostasis, but their use and interpretation require caution and are often far from straightforward
Organs by design: can bioprinting meet self-organization?
No full textPURPOSE OF REVIEW: Engineering functional organs starting from stem or progenitor cells holds promise to address the urgent need for organ transplants. However, to date, the development of complex organ structures remains an open challenge. RECENT FINDINGS: Among multiple approaches to organ regeneration that are being investigated, two main directions can be identified, namely the patterned deposition of cells to impose specific structures, using bioprinting technologies, and (ii) the spontaneous development of organoids, according to principles of self-organization. In this review, we shortly describe the advantages and limitations of these paradigms and we discuss how they can synergize their positive features to better control and robustly develop organs from stem cells, toward organogenesis by design. SUMMARY: The outlined possibilities to bring together tools and concepts of bioprinting and self-organization will be relevant not only to generate implantable organs, but also to dissect fundamental mechanisms of organogenesis and to test therapeutic strategies in modeled pathological settings
Hypoxia negatively affects senescence in osteoclasts and delays osteoclastogenesis
No full textCellular senescence, that is, the withdrawal from the cell cycle, combined with the acquirement of the senescence associated secretory phenotype has important roles during health and disease and is essential for tissue remodeling during embryonic development. Osteoclasts are multinucleated cells, responsible for bone resorption, and cell cycle arrest during osteoclastogenesis is well recognized. Therefore, the aim of this study was to investigate whether these cells should be considered senescent and to assess the influence of hypoxia on their potential senescence status. Osteoclastogenesis and bone resorption capacity of osteoclasts, cultured from CD14+ monocytes, were evaluated in two oxygen concentrations, normoxia (21% O2 ) and hypoxia (5% O2 ). Osteoclasts were profiled by using specific staining for proliferation and senescence markers, qPCR of a number of osteoclast and senescence-related genes and a bone resorption assay. Results show that during in vitro osteoclastogenesis, osteoclasts heterogeneously obtain a senescent phenotype. Furthermore, osteoclastogenesis was delayed at hypoxic compared to normoxic conditions, without negatively affecting the bone resorption capacity. It is concluded that osteoclasts can be considered senescent, although senescence is not uniformly present in the osteoclast population. Hypoxia negatively affects the expression of some senescence markers. Based on the direct relationship between senescence and osteoclastogenesis, it is tempting to hypothesize that contents of the so-called senescence associated secretory phenotype (SASP) not only play a functional role in matrix resorption, but also may regulate osteoclastogenesis
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