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Osteoarthritis and Cartilage Dec 2018The objective of this study was to evaluate the effect of full-thickness chondral defects on intratissue deformation patterns and matrix constituents in an experimental...
OBJECTIVE
The objective of this study was to evaluate the effect of full-thickness chondral defects on intratissue deformation patterns and matrix constituents in an experimental model mimicking in vivo cartilage-on-cartilage contact conditions.
DESIGN
Pairs of bovine osteochondral explants, in a unique cartilage-on-cartilage model system, were compressed uniaxially by 350 N during 2 s loading and 1.4 s unloading cycles (≈1700 repetitions). Tissue deformations under quasi-steady state load deformation response were measured with displacement encoded imaging with stimulated echoes (DENSE) in a 9.4 T magnetic resonance imaging (MRI) scanner. Pre- and post-loading, T, T and T relaxation time maps were measured. We analyzed differences in strain patterns and relaxation times between intact cartilage (n = 8) and cartilage in which a full-thickness and critical sized defect was created (n = 8).
RESULTS
Under compressive loading, strain magnitudes were elevated at the defect rim, with elevated tensile and compressive principal strains (Δϵ = 4.2%, P = 0.02; Δϵ = -4.3%, P = 0.02) and maximum shear strain at the defect rim (Δγ = 4.4%, P = 0.007). The opposing cartilage showed minimal increase in strain patterns at contact with the defect rim but decreased strains opposing the defect. After defect creation, T, T and T relaxation times were elevated at the defect rim only. Following loading, the overall relaxations times of the defect tissue and especially at the rim, increased compared to intact cartilage.
CONCLUSIONS
This study demonstrates that the local biomechanical changes occurring after defect creation may induce tissue damage by increasing shear strains and depletion of cartilage constituents at the defect rim under compressive loading.
Topics: Animals; Cartilage, Articular; Cattle; Femur; Magnetic Resonance Imaging; Stress, Mechanical; Weight-Bearing
PubMed: 30195045
DOI: 10.1016/j.joca.2018.08.013 -
Advanced Science (Weinheim,... Sep 2023The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular... (Review)
Review
The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular cartilage, stem cells are characterized by overlapping lineages and uneven effectiveness. Within the first 12 weeks after trauma, the articular inflammatory microenvironment (AIME) plays a decisive role in determining the fate of stem cells and cartilage. The development of fibrocartilage and osteophyte hyperplasia is an adverse outcome of chronic inflammation, which results from an imbalance in the AIME during the cartilage tissue repair process. In this review, the sources for the different types of stem cells and their fate are summarized. The main pathophysiological events that occur within the AIME as well as their protagonists are also discussed. Additionally, regulatory strategies that may guide the fate of stem cells within the AIME are proposed. Finally, strategies that provide insight into AIME pathophysiology are discussed and the design of new materials that match the post-traumatic progress of AIME pathophysiology in a spatial and temporal manner is guided. Thus, by regulating an appropriately modified inflammatory microenvironment, efficient stem cell-mediated tissue repair may be achieved.
Topics: Humans; Regeneration; Tissue Engineering; Stem Cells; Cartilage, Articular; Wound Healing; Arthritis
PubMed: 37518822
DOI: 10.1002/advs.202207715 -
Journal of the Mechanical Behavior of... Oct 2019Cartilage breaks down during mechanically-mediated osteoarthritis (OA). While previous research has begun to elucidate mechanical, structural and cellular damage in...
Cartilage breaks down during mechanically-mediated osteoarthritis (OA). While previous research has begun to elucidate mechanical, structural and cellular damage in response to cyclic loading, gaps remain in our understanding of the link between cyclic cartilage loading and OA-like mechanical damage. Thus, the aim of this study was to quantify irreversible cartilage damage in response to cyclic loading. A novel in vitro model of damage through cartilage-on-cartilage cyclic loading was established. Cartilage was loaded at 1 Hz to two different doses (10,000 or 50,000 cycles) between -6.0 ± 0.2 MPa and -10.3 ± 0.2 MPa 1st Piola-Kirchhoff stress. After loading, mechanical damage (altered mechanical properties: elastic moduli and dissipated energy) and structural damage (surface damage and specimen thickness) were quantified. Linear and tangential moduli were determined by fitting the loading portion of the stress-strain curves. Dissipated energy was calculated from the area between loading and unloading stress-strain curves. Specimen thickness was measured both before and after loading. Surface damage was assessed by staining samples with India ink, then imaging the articular surface. Cyclic loading resulted in dose-dependent decreases in linear and tangential moduli, energy dissipation, thickness, and intact area. Collectively, these results show that cartilage damage can be initiated by mechanical loading alone in vitro, suggesting that cyclic loading can cause in vivo damage. This study demonstrated that with increased number of cycles, cartilage undergoes both tissue softening and structural damage. These findings are a first step towards characterizing the cartilage response to cyclic loading, which can ultimately provide important insight for delaying the initiation and slowing the progression of OA.
Topics: Animals; Biomechanical Phenomena; Cartilage, Articular; Materials Testing; Swine; Weight-Bearing
PubMed: 31280053
DOI: 10.1016/j.jmbbm.2019.06.023 -
Osteoarthritis and Cartilage Oct 2020Quantitative, micrometer length scale assessment of human articular cartilage is essential to enable progress toward new functional tissue engineering approaches,...
OBJECTIVE
Quantitative, micrometer length scale assessment of human articular cartilage is essential to enable progress toward new functional tissue engineering approaches, including utilization of emerging 3D bioprinting technologies, and for improved computational modeling of the osteochondral unit. Thus the objective of this study was to characterize the structural organization, material properties, and chemical composition of human skeletally mature articular cartilage with respect to depth and defined morphological features: normal to the articulating surface, parallel to the split-line, and transverse to the split-line.
METHOD
Three samples from the lateral femoral condyles of 4 healthy adult donors (55-61 years old) were evaluated via histology, second harmonic generation, microindentation, and Raman spectroscopy. All metrics were evaluated as a function of depth and direction relative to the split-line.
RESULTS
All donors presented with intact and healthy tissue. Collagen fiber orientation varied significantly between testing directions and with increasing depth from the articular surface. Both compressive and tensile modulus increased significantly with depth and differed across the middle and deep zones and depended on orthogonal direction relative to the split-line. Similarly, matrix components varied with both depth and direction, where chondroitin sulfate steadily increased with depth while collagen prevalence was highest in the surface layer.
CONCLUSIONS
Microscale measurements of human articular cartilage demonstrate that properties are both depth-dependent and orthotropic and depend on the underlying tissue structure and composition. These findings improve upon existing knowledge establishing more accurate measurements, with greater degree of depth and spatial specificity, as inputs for tissue engineering and computational modeling.
Topics: Biomechanical Phenomena; Cartilage, Articular; Female; Humans; Male; Middle Aged; Second Harmonic Generation Microscopy; Spectrum Analysis, Raman
PubMed: 32645403
DOI: 10.1016/j.joca.2020.06.007 -
Osteoarthritis and Cartilage Feb 2017To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness...
OBJECTIVE
To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects.
DESIGN
IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively.
RESULTS
Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction.
CONCLUSION
Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation.
Topics: Animals; Bone and Bones; Cartilage, Articular; Dose-Response Relationship, Drug; Insulin-Like Growth Factor I; Rabbits; Real-Time Polymerase Chain Reaction
PubMed: 27662821
DOI: 10.1016/j.joca.2016.09.010 -
Osteoarthritis and Cartilage Jun 2018Osteoarthritis results from the degradation of articular cartilage and is one of the leading global causes of pain and immobility. Cartilage has a limited capacity for... (Review)
Review
Osteoarthritis results from the degradation of articular cartilage and is one of the leading global causes of pain and immobility. Cartilage has a limited capacity for self-repair. While repair can be enhanced through surgical intervention, current methods often generate inferior fibrocartilage and repair is transient. The development of tissue engineering strategies to improve repair outcomes is an active area of research. While small animal models such as rodents and rabbits are often used in early pre-clinical work, larger animals that better recapitulate the anatomy and loading of the human joint are required for late-stage preclinical evaluation. Because of their physiological similarities to humans, and low cost relative to other large animals, sheep are routinely used in orthopedic research, including cartilage repair studies. In recent years, there has been considerable research investment into the development of cartilage repair strategies that utilize mesenchymal stem/stromal cells (MSC). In contrast to autologous chondrocytes derived from biopsies of articular cartilage, MSC offer some benefits including greater expansion capacity and elimination of the risk of morbidity at the cartilage biopsy site. The disadvantages of MSC are related to the challenges of inducing and maintaining a stable chondrocyte-like cell population capable of generating hyaline cartilage. Ovine MSC (oMSC) biology and their utility in sheep cartilage repair models have not been reviewed. Herein, we review the biological properties of MSC derived from sheep tissues, and the use of these cells to study articular cartilage repair in this large animal model.
Topics: Animals; Cartilage, Articular; Cells, Cultured; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Models, Animal; Osteoarthritis; Sheep
PubMed: 29580978
DOI: 10.1016/j.joca.2018.03.006 -
Journal of Cellular and Molecular... Dec 2014Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is... (Review)
Review
Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field.
Topics: Cartilage, Articular; Cell- and Tissue-Based Therapy; Chondrocytes; Chondrogenesis; Extracellular Matrix Proteins; Humans; Mesenchymal Stem Cells; Models, Biological; Osteoarthritis; Regeneration
PubMed: 25353372
DOI: 10.1111/jcmm.12378 -
Journal of Anatomy Jul 1997The chondrocyte and its pericellular microenvironment together represent the chondron, historically considered the primary structural, functional and metabolic unit of... (Review)
Review
The chondrocyte and its pericellular microenvironment together represent the chondron, historically considered the primary structural, functional and metabolic unit of articular and other hyaline cartilages. This review summarises research over the last 10 years to establish the molecular anatomy, functional properties and metabolic contribution of the chondron in articular cartilage homeostasis, and its failure during the initiation and progression of degenerative osteoarthritis.
Topics: Animals; Cartilage, Articular; Collagen; Extracellular Matrix; Humans; Microscopy, Confocal; Osteoarthritis
PubMed: 9279653
DOI: 10.1046/j.1469-7580.1997.19110001.x -
Croatian Medical Journal Jun 2011Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the... (Review)
Review
Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration.
Topics: Animals; Cartilage, Articular; Chondrocytes; Gene Transfer Techniques; Genetic Engineering; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; NIH 3T3 Cells
PubMed: 21674822
DOI: 10.3325/cmj.2011.52.245 -
International Journal of Molecular... Oct 2023This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to... (Review)
Review
This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to image the structure and associated functions of articular cartilage but, instead, to devise methods for generating non-invasive, function-depicting images with quantitative information that is useful for detecting the early, pre-clinical stage of diseases such as primary or post-traumatic osteoarthritis (OA/PTOA). In this context, this review summarizes (a) the structure and function of articular cartilage as a molecular imaging target, (b) quantitative MRI for non-invasive assessment of articular cartilage composition, microstructure, and function with the current state of medical diagnostic imaging, (c), non-destructive imaging methods, (c) non-destructive quantitative articular cartilage live-imaging methods, (d) artificial intelligence (AI) classification of degeneration and prediction of OA progression, and (e) our contribution to this field, which is an AI-supported, non-destructive quantitative optical biopsy for early disease detection that operates on a digital tissue architectural fingerprint. Collectively, this review shows that articular cartilage imaging has undergone profound changes in the purpose and expectations for which cartilage imaging is used; the image is becoming an AI-usable biomarker with non-invasive quantitative functional information. This may aid in the development of translational diagnostic applications and preventive or early therapeutic interventions that are yet beyond our reach.
Topics: Humans; Cartilage, Articular; Artificial Intelligence; Osteoarthritis; Magnetic Resonance Imaging; Research
PubMed: 37834422
DOI: 10.3390/ijms241914974