Review

Authors: Eleftherios A Makris, Andreas H Gomoll, Konstantinos N Malizos...

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

Topics: Biocompatible Materials; Biological Factors; Cartilage, Articular; Chondrocytes; Humans; Knee Injuries; Knee Joint; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Prospective Studies; Randomized Controlled Trials as Topic; Regeneration; Tissue Engineering; Tissue Scaffolds; Wound Healing

PubMed: 25247412
DOI: 10.1038/nrrheum.2014.157

Review

Authors: Song Chen, Peiliang Fu, Haishan Wu...

The degradation of cartilage in the human body is impacted by aging, disease, genetic predisposition and continued insults resulting from daily activity. The burden of cartilage defects (osteoarthritis, rheumatoid arthritis, intervertebral disc damage, knee replacement surgeries, etc.) is daunting in light of substantial economic and social stresses. This review strives to broaden the scope of regenerative medicine and tissue engineering approaches used for cartilage repair by comparing and contrasting the anatomical and functional nature of the meniscus, articular cartilage (AC) and nucleus pulposus (NP). Many review papers have provided detailed evaluations of these cartilages and cartilage-like tissues individually but none have comprehensively examined the parallels and inconsistencies in signaling, genetic expression and extracellular matrix composition between tissues. For the first time, this review outlines the importance of understanding these three tissues as unique entities, providing a comparative analysis of anatomy, ultrastructure, biochemistry and function for each tissue. This novel approach highlights the similarities and differences between tissues, progressing research toward an understanding of what defines each tissue as distinctive. The goal of this paper is to provide researchers with the fundamental knowledge to correctly engineer the meniscus, AC and NP without inadvertently developing the wrong tissue function or biochemistry.

Topics: Animals; Biomechanical Phenomena; Cartilage, Articular; Collagen; Humans; Meniscus; Nucleus Pulposus; Regeneration; Tissue Engineering

PubMed: 28413859
DOI: 10.1007/s00441-017-2613-0

Review

Authors: Rebekah S Decker, Eiki Koyama, Maurizio Pacifici...

Articular cartilage has obvious and fundamental roles in joint function and body movement. Much is known about its organization, extracellular matrix, and phenotypic properties of its cells, but less is known about its developmental biology. Incipient articular cartilage in late embryos and neonates is a thin tissue with scanty matrix and small cells, while adult tissue is thick and zonal and contains large cells and abundant matrix. What remains unclear is not only how incipient articular cartilage forms, but how it then grows and matures into a functional, complex, and multifaceted structure. This review focuses on recent and exciting discoveries on the developmental biology and growth of articular cartilage, frames them within the context of classic studies, and points to lingering questions and research goals. Advances in this research area will have significant relevance to basic science, and also considerable translational value to design superior cartilage repair and regeneration strategies.

Topics: Animals; Cartilage, Articular; Cell Lineage; Chondrocytes; Extracellular Matrix; Guided Tissue Regeneration; Humans

PubMed: 26408155
DOI: 10.1007/s11914-015-0290-z

Review

Authors: Rebekah S Decker, Eiki Koyama, Maurizio Pacifici...

Limb synovial joints are intricate structures composed of articular cartilage, synovial membranes, ligaments and an articular capsule. Together, these tissues give each joint its unique shape, organization and biomechanical function. Articular cartilage itself is rather complex and organized in distinct zones, including the superficial zone that produces lubricants and contains stem/progenitor cells. For many years there has been great interest in deciphering the mechanisms by which the joints form and come to acquire such unique structural features and diversity. Decades ago, classic embryologists discovered that the first overt sign of joint formation at each prescribed limb site was the appearance of a dense and compact population of mesenchymal cells collectively called the interzone. Work carried out since then by several groups has provided evidence that the interzone cells actively participate in joint tissue formation over developmental time. This minireview provides a succinct but comprehensive description of the many important recent advances in this field of research. These include studies using various conditional reporter mice to genetically trace and track the origin, fate and possible function of joint progenitor cells; studies on the involvement and roles in signaling pathways and transcription factors in joint cell determination and functioning; and studies using advanced methods of gene expression analyses to uncover novel genetic determinants of joint formation and diversity. The overall advances are impressive, and the findings are not only of obvious interest and importance but also have major implications in the conception of future translational medicine tools to repair and regenerate defective, overused or aging joints.

Topics: Animals; Cartilage, Articular; Cell Differentiation; Chondrogenesis; Embryonic Stem Cells; Humans; Joint Capsule; Joints; Morphogenesis

PubMed: 25172830
DOI: 10.1016/j.matbio.2014.08.006

Review

Authors: K L Caldwell, J Wang

Clinical efforts to repair damaged articular cartilage (AC) currently face major obstacles due to limited intrinsic repair capacity of the tissue and unsuccessful biological interventions. This highlights a need for better therapeutic strategies. This review summarizes the recent advances in the field of cell-based AC repair. In both animals and humans, AC defects that penetrate into the subchondral bone marrow are mainly filled with fibrocartilaginous tissue through the differentiation of bone marrow mesenchymal stem cells (MSCs), followed by degeneration of repaired cartilage and osteoarthritis (OA). Cell therapy and tissue engineering techniques using culture-expanded chondrocytes, bone marrow MSCs, or pluripotent stem cells with chondroinductive growth factors may generate cartilaginous tissue in AC defects but do not form hyaline cartilage-based articular surface because repair cells often lose chondrogenic activity or result in chondrocyte hypertrophy. The new evidence that AC and synovium develop from the same pool of precursors with similar gene profiles and that synovium-derived chondrocytes have stable chondrogenic activity has promoted use of synovium as a new cell source for AC repair. The recent finding that NFAT1 and NFAT2 transcription factors (TFs) inhibit chondrocyte hypertrophy and maintain metabolic balance in AC is a significant advance in the field of AC repair. The use of synovial MSCs and discovery of upstream transcriptional regulators that help maintain the AC phenotype have opened new avenues to improve the outcome of AC regeneration.

Topics: Cartilage, Articular; Cell- and Tissue-Based Therapy; Chondrocytes; Chondrogenesis; Humans; Mesenchymal Stem Cell Transplantation; NFATC Transcription Factors; Osteoarthritis; Regeneration; Synovial Membrane; Tissue Engineering

PubMed: 25450846
DOI: 10.1016/j.joca.2014.11.004

Review

Authors: José G Raya

Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity and to the collagen architecture through the fractional anisotropy. However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (∼40 ms at 3 Tesla) and the high resolution needed (0.5-0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications.

Topics: Biomechanical Phenomena; Cartilage, Articular; Contrast Media; Diffusion Magnetic Resonance Imaging; Humans; Osteoarthritis

PubMed: 25865215
DOI: 10.1002/jmri.24767

Review

Authors: Holger Jahr, Csaba Matta, Ali Mobasheri...

Articular cartilage is a unique load-bearing connective tissue with a low intrinsic capacity for repair and regeneration. Its avascularity makes it relatively hypoxic and its unique extracellular matrix is enriched with cations, which increases the interstitial fluid osmolarity. Several physicochemical and biomechanical stimuli are reported to influence chondrocyte metabolism and may be utilized for regenerative medical approaches. In this review article, we summarize the most relevant stimuli and describe how ion channels may contribute to cartilage homeostasis, with special emphasis on intracellular signaling pathways. We specifically focus on the role of calcium signaling as an essential mechanotransduction component and highlight the role of phosphatase signaling in this context.

Topics: Cartilage, Articular; Chondrocytes; Humans; Mechanotransduction, Cellular; Regeneration; Stress, Mechanical; Weight-Bearing; Wound Healing

PubMed: 25828845
DOI: 10.1007/s11926-014-0493-9

Review

Authors: Susanna Chubinskaya, Dominik Haudenschild, Seth Gasser...

Osteoarthritis affects millions of people worldwide, is associated with joint stiffness and pain, and often causes significant disability and loss of productivity. Osteoarthritis is believed to occur as a result of ordinary "wear and tear" on joints during the course of normal activities of daily living. Posttraumatic osteoarthritis is a particular subset of osteoarthritis that occurs after a joint injury. Developing clinically relevant animal models will allow investigators to delineate the causes of posttraumatic osteoarthritis and develop means to slow or prevent its development after joint injury. Chondroprotectant compounds, which attack the degenerative pathways at a variety of steps, are being developed in an effort to prevent posttraumatic osteoarthritis and offer great promise. Often times, cartilage degradation after joint injury occurs despite our best efforts. When this happens, there are several evolving techniques that offer at least short-term relief from the effects of posttraumatic osteoarthritis. Occasionally, these traumatic lesions are so large that dramatic steps must be taken in an attempt to restore articular congruity and joint stability. Fresh osteochondral allografts have been used in these settings and offer the possibility of joint preservation. For patients presenting with neglected displaced intra-articular fractures that have healed, intra-articular osteotomy techniques are being developed in an effort to restore joint congruity and function. This article reviews the results of a newly developed animal model of posttraumatic osteoarthritis, several promising chondroprotectant compounds, and also cartilage techniques that are used when degenerative cartilage lesions develop after joint injury.

Topics: Anti-Inflammatory Agents; Cartilage, Articular; Combined Modality Therapy; Fractures, Cartilage; Humans; Osteoarthritis; Osteotomy; Plastic Surgery Procedures

PubMed: 26584267
DOI: 10.1097/BOT.0000000000000462

Review

Authors: Gustav Andreisek, Markus Weiger

T2* mapping is a relatively new method for the compositional assessment of the articular cartilage. Typically, a multigradient echo or an ultrashort echo time imaging technique with a range of short and very short echo times is used. In most studies, imaging is performed at a high field strength, that is, 3 and 7 T. Postprocessing includes exponential fitting of relaxation decay and manual region-of-interest-based measurements of T2* times on T2* maps. Detailed analyses of T2* times of articular cartilage have shown distinct T2* components with shorter and longer T2* times. Moreover, there is a zonal distribution with a significant depthwise gradient of T2*, with relatively short times near the osteochondral junction and relatively long times at the cartilage's surface. T2* times of normal articular cartilage at the knee are, when averaged over the whole cartilage thickness and using monoexponential fitting, approximately 20 milliseconds. The results of recent studies have shown a good test-retest as well as interreader and intrareader reliabilities for T2* mapping. This article provides a descriptive review of the current literature, briefly discusses the technique itself, and provides an outlook on future research questions and possible clinical applications.

Topics: Cartilage Diseases; Cartilage, Articular; Evidence-Based Medicine; Humans; Image Enhancement; Joint Diseases; Magnetic Resonance Imaging

PubMed: 24056113
DOI: 10.1097/RLI.0b013e3182a574e1

Review

Authors: Domenico Albano, Umberto Viglino, Francesco Esposito...

This review examines the latest advancements in compositional and quantitative cartilage MRI techniques, addressing both their potential and challenges. The integration of these advancements promises to improve disease detection, treatment monitoring, and overall patient care. We want to highlight the pivotal task of translating these techniques into widespread clinical use, the transition of cartilage MRI from technical validation to clinical application, emphasizing its critical role in identifying early signs of degenerative and inflammatory joint diseases. Recognizing these changes early may enable informed treatment decisions, thereby facilitating personalized medicine approaches. The evolving landscape of cartilage MRI underscores its increasing importance in clinical practice, offering valuable insights for patient management and therapeutic interventions. This review aims to discuss the old evidence and new insights about the evaluation of articular cartilage through MRI, with an update on the most recent literature published on novel quantitative sequences.

Topics: Humans; Cartilage, Articular; Magnetic Resonance Imaging

PubMed: 39058044
DOI: 10.3390/tomography10070072