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Articular cartilage
BASIC SCIENCE
Articular cartilage
hyaline cartilage and the chondrocytes are evenly distributed in lacunae. Hyaline cartilage provides the surface coverage of articular surfaces and is also found in the tip of the nose. Elastic cartilage is more opaque and has a yellowish appearance. It is identified microscopically by clearly visible darkstaining elastic fibres embedded in ground substance and it is the presence of these fibres that is the most reliable means for differentiating elastic from hyaline cartilage. Perichondrium is also typically found around elastic cartilage. It is more elastic than other cartilage types and can be found in the epiglottis and external ear, where elasticity of tissues is essential. Fibrocartilage contains fine collagen fibres arranged in layered arrays. Compared to the regimented appearance of hyaline cartilage, fibrocartilage appears more disorganized, with gaps between the lacunae and collagen fibre bundles. It is this open, more flexible structure that makes fibrocartilage a good shockabsorbing material, a property required for the pubic symphysis and intervertebral discs. Fibrous cartilage in the pubic symphysis has a tighter construction, reminiscent of a dense connective tissue with lacunae, whereas the structure of the intervertebral discs is more open. Fibrocartilage is also found in the menisci of the knee.
Deborah Lees Paul Partington
Abstract Cartilage is a resilient structure that is both strong and flexible, and is found in many parts of the body. The type of collagen present in the structure determines the type and properties of the cartilage. The structure of articular cartilage is important for loading responses and lubrication, and a typical curve can be demonstrated for both stressstrain and creep-time properties. Osteoarthritis is a common posttraumatic consequence of articular cartilage injury as well as a wellknown consequence of the ageing process. Different approaches to managing cartilage loss or injury have been explored and include steroid and hyaluronic injections, chondroplasty and chondrocyte transfer, with varying success.
Keywords articular; cartilage; chondrocyte; collagen
Introduction Structure and characteristics of articular cartilage
Cartilage is found in many structures throughout the body and negotiates the balance between the need for structural support and flexibility in a unique fashion. It takes on different forms depending on the particular demand of the structure, and whilst the basic components of extracellular matrix and cells remain consistent, the proportions of these components vary within the cartilage subtypes. Cartilage is formed by chondroblasts, which are mesenchymal in origin and which later mature into chondrocytes. Chondroblasts are thus typically found under the perichondrium along the border of the cartilage plates where new appositional growth occurs, although cartilage can also expand via interstitial growth. In epiphyseal plates, chondrocytes enlarge and divide during maturation to form single or multicellular lacunae arranged in linear stacks. There are five recognized types of cartilage (with typical locations in brackets): hyaline (articular), fibroelastic (meniscus), fibrocartilage (bony insertion of tendon/ligament), elastic (trachea) and physeal cartilage (physis). Healthy hyaline cartilage has a smooth, uniform, glassy appearance and is bluish-white in colour, but may loose some of these characteristics with age. The optical density of the collagen fibres approximates that of the extracellular matrix and they are therefore difficult to differentiate under light microscopy as structures separate from the matrix. Perichondrium covers
Articular cartilage demonstrates both a fluid and a solid phase, which determines its mechanical properties. The fluid phase consists of water and electrolytes and fills the gaps between the solid matrix. This fluid accounts for the majority of the wet weight of articular cartilage. The solid phase contains chondrocytes and an extracellular matrix consisting of proteoglycans, collagen fibres and non-collagenous protein. Type II collagen accounts for 90e95% of the collagen content, with the remainder made up of a variety of other collagen types. The chondrocytes make up the cellular component and they produce and maintain the extracellular matrix. Proteoglycans account for approximately 10e15% of the cartilage structure and function to attract water, thereby improving the overall compressive strength. Proteoglycans are predominantly protein-based molecules, mostly concentrated in the middle layer and less concentrated in the deeper layers. They are made up of repeating disaccharide units (glycosaminoglycans), which are of two main types: chondroitin sulphate and keratin sulphate. Attached carboxyl and sulphate groups give the glycosaminoglycans (GAGs) a high negative charge and as a result they attract cations and water, thereby increasing the osmotic pressure of the structure. GAGs combine with a protein core to form a proteoglycan aggrecan molecule (hydrophilic), which in turn binds to hyaluronic acid (HA) to form a proteoglycan aggregate (macromolecule), and the bond is stabilized by a link protein. The proteoglycans weave between the collagen fibres to create a solid lattice with the ability to control water movement within the structure. Water accounts for 65e80% of the articular cartilage mass, with the highest proportion being near the surface. The high water content of articular cartilage provides incompressibility properties, and when combined with its characteristic structural organization this facilitates its stress-shielding properties. The water content reduces with ageing, leading to increased permeability, reduced strength and a reduced Young’s modulus
Deborah Lees M.Tech(Chiropractic) MBBS MRCS Trauma & Orthopaedic Surgery Specialty Trainee, Northumbria Healthcare NHS Foundation Trust, Orthopaedic Department, Wansbeck General Hospital, Ashington, UK. Paul Partington FRCS FRCS (Trauma & Orthopaedics) Trauma & Orthopaedic Surgery Consultant, Northumbria Healthcare NHS Foundation Trust, Orthopaedic Department, Wansbeck General Hospital, Ashington, UK.
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BASIC SCIENCE
of elasticity. Ageing also results in increases in chondrocyte size, protein content, stiffness and keratin sulphate to chondroitin sulphate ratio, in combination with a decrease in absolute cell number and proteoglycan size. As the ageing process progresses, type X collagen is expressed, alkaline phosphatase is produced, matrix vesicles develop and matrix calcification is subsequently seen on radiographs as subchondral sclerosis. Degradative enzymes (matrix metaloproteinases) maintain turnover of the matrix by degradation of the proteoglycan aggregates and collagen. Tissue-induced metalloproteinase inhibitors (TIMPs) regulate the matrix degradation by binding to the matrix proteins and also maintain the avascular nature of the cartilage by preventing vascular endothelial migration. Articular cartilage provides a low friction surface that is wear resistant and the layers help to distribute weight in load-bearing joints. Articular cartilage consists of four zones and the tidemark (Figure 1 and Table 1): the zones are characterised on the basis of the chondrocyte shape and the orientation of the Type II collagen.
transforming growth factor beta (TGF-B: proteoglycan synthesis), basic fibroblastic growth factor (b-FGF: DNA synthesis in chondrocytes) and insulin growth factore1 (IGF-1: DNA and cartilage matrix synthesis). Parathyroid hormone and thyroxine stimulate matrix synthesis.
Mechanical properties and stress resistance The mechanical properties of articular cartilage can exhibit great variation as result of its structural complexity and organization. Cartilage is biphasic (fluid and solid phase), visco-elastic in tension (exhibits a stress-strain relationship that is dependent on the load and the rate by which the load is applied) and anisotropic (possesses different mechanical properties depending on the direction of the applied load). Cartilage also undergoes creep (the phenomenon of progressive deformation under constant load) and stress-relaxation (a gradual decrease in stress with time under a constant deformation or strain). These properties are made possible by movement of water and macromolecules within cartilage, as up to 70% of the water content is mobile. Whilst water has the ability to move freely, the macromolecules produce a frictional drag under high load, which restricts the flow of water and stiffens the cartilage structure. Due to the arrangement of the collagen fibres, collagen-proteoglycan relationships and cross-links, directional loading can elicit different responses depending on the direction. In tension, the structural organization of the components is altered, resulting in increased water permeability and reduced compressive stiffness. When articular cartilage specimens are subject to a constant strain, the tensile stress-strain behaviour is non-linear. The characteristic graph curve results from an initial straightening of the slack fibres along with an increasing number of fibres being recruited. The increasing number of collagen fibrils
Metabolism, nourishment and the role of cartilage specific growth factors Articular cartilage is avascular and relies on the diffusion of nutrients from the synovial fluid at its surface and from the subchondral bone at its deep surface. The metabolic rate is very low, with adenosine triphosphate (ATP) production via the lactic acid pathway. The extracellular matrix adjacent to the cellular elements has a relatively high turnover when compared to proteoglycans (weeks to months) and collagen (several years). Various growth factors have been found to play a role in repair, proteoglycan synthesis and chondrocyte DNA synthesis. These include platelet-derived growth factor (PDGF: repair), Chondrocytes
Collagen
Proteogylcans
Zone I Superficial Zone II
Intermediate
Zone III Deep
Tidemark Zone IV Calcified
Subchondral bone
Hydroxyapatite H d crystals t s
Figure 1 Zones of articular cartilage. Zone 1: Flattened chondrocytes, collagen fibres parallel to joint, sparse proteoglycans. Zone II: Round chondrocytes, oblique/random collagen fibres and plentiful proteoglycans. Zone III: Thickest layer, columns of chondrocytes, collagen bundles perpendicular to joint, cross the tidemark and are anchored into subchondral bone, highest proteoglycan content. Zone IV: Type X collagen present and hydroxyapatite crystals anchor cartilage to subchondral bone.
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Summary of the characteristics of the zones of articular cartilage Zone
Cellular components
Collagen components
Proteoglycan components
Additional features
Superficial I (gliding)
Flattened chondrocytes 1e3 layers thick. Exhibit macrophage-type behaviour. Round chondrocytes.
Lamina splendins. Condensed fibres parallel to joint e resists shear stress.
Sparse.
Oblique or random orientation.
Plentiful.
Thinnest layer. Progenitor cells present. May function as a barrier layer regulating molecular movement. Thickest layer. Allows transition from superficial shear to compression stress resistance. Largest part of articular cartilage. Resists compression.
Intermediate II (transitional)
Deep Layer III (radial)
Tidemark
Calcified Zone IV
Round chondrocytes arranged in columns.
Bundles of fibres Highest content anchored into the in all the layers. underlying bone, perpendicular to joint. Crosses tidemark. Only found in joints e cell free layer. Most prominent in mature joints (non-growing). Separates the true articular cartilage from the cartilage anlarge (childhood growth remnant from endochondral ossification). Divides superficial uncalcified layers from deeper calcified layers. Division between chondrocyte nutritional sources. Type X collagen. Hydroxyapatite crystals anchor the cartilage to the subchondral bone.
Subchondral bone Table 1
film formation and efflux of fluid from cartilage. Synovial fluid is essentially an ultra-filtrate of blood plasma. It is a highly viscous, clear, pale yellow liquid secreted by the fibroblast-like type B synovial cells, and mostly consists of hyaluronate (hyaluronic acid) and lubricin (glycoprotein). The volume varies from joint to joint, as does the actual composition. There are two broad categories of lubrication: boundary and fluid-film lubrication, and these theories have been adapted to explain human joint lubrication. Boundary lubrication is most important at rest. When loaded, a thin layer of lubricant fluid prevents direct articular contact. If large loads are maintained for long time periods, the fluid film is depleted except for a layer of lubricant molecules that are chemically attached to the surfaces, thereby creating a boundary layer. This boundary layer has low shear strength and thus offers lower friction than unlubricated surfaces. In synovial joints, lubrican is the lubricating glycoprotein. The lubrican molecules create a monolayer on each articulating surface, which reduces surface friction and prevents articular wear. Hydrodynamic lubrication, squeeze-film lubrication and elastohydrodynamic lubrication are all types of fluid-film lubrication. Hydrodynamic lubrication occurs when the surfaces are at an angle to each other and one surface slides over another with the bearing surface separated by a wedge of fluid. As the surfaces slide over one another, a layer of fluid is dragged through a narrowing wedge-shaped gap. The action creates a hydrodynamic pressure in the fluid, creating a lift force that keeps the sliding surfaces separated. The fluid film ensures the two sliding
resisting the tension force, as the slack fibrils are first straightened and then stretched with the increasing strain, causes the typical curve shape. The characteristic curve (Figure 2) can be separated into two regions: 1) the toe region and 2) the linear region. The toe region is where the coiled collagen fibrils are becoming straightened and are beginning to resist the applied strain. The linear region is where all the collagen fibrils are stretched and are all resisting strain. Creep deformation (Figure 3) occurs as fluid is forced from the tissue during loading. Initially, there is rapid deformation and fluid is rapidly exuded, and flow gradually slows as the remaining amount of fluid diminishes, so the rate of exudation slows until equilibrium is achieved and the fluid flow stops. Physiological stress inhibits chondrolysis and stimulates matrix synthesis, whereas excessive stress promotes chondrolysis and inhibits matrix synthesis. Primary cilia present on chondrocytes and osteoblasts act as a mechanosensory system, with integrin aiding in the transduction of mechanical signals. Immobilization results in cartilage softening, proteoglycan loss and overall reduction of the cartilage thickness. Repetitive loading results in an initial increase in cartilage thickness and proteoglycan content, but once this progresses to strenuous loading, the cartilage starts to thin and the proteoglycan content decreases.
Lubrication and wear One of the functions of articular cartilage is joint lubrication. Cartilage has an extremely low co-efficient of friction, which can be further reduced by elastic deformation, synovial fluid, fluid-
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In reality, however, none of the lubricating mechanisms can individually explain joint lubrication, and synovial joints demonstrate aspects of both boundary and fluid-film lubrication. The prominent mechanism at any single moment is dependent on the current conditions. During range of movement, at the areas that are in close contact, boundary lubrication is characteristic, with fluid-film lubrication seen throughout the remainder of the bearing surface. Boundary and elastohydrodynamic lubrication occur during movement, and a further two types of lubrication (weeping/self-lubrication and boosted lubrication) are thought to occur. In weeping lubrication, fluid is driven both under and in front of the loading surface until maximum compression load is reached, and as the load is lifted the cartilage reforms as the water is re-absorbed. Boosted lubrication involves separation of the lubricating fluid, where the water is driven into the superficial cartilage layers, with concentrated hyaluronic acid remaining on the joint surface. These puddles are described as pools of fluid trapped by contacting areas of the bearing surfaces.
Lin e
ar
Tensile Stress
re g
ion
Stress-strain curve for articular cartilage using a constant strain rate
Toe
on
regi
Strain Figure 2 Stress-strain graph of articular cartilage.
Healing process Articular cartilage has slow growth potential and very poor regenerative capacity due to the lack of direct blood supply; hence the high incidence of post-traumatic degeneration, ageing and condition-specific pathology. Cartilage lacerations superficial to the tidemark do not heal due to the avascular nature of the structure, despite local proliferation of chondrocytes. Lacerations that penetrate deep to the tidemark are able to elicit a healing response via haematoma, endothelial ingrowth and marrow mesenchymal cell migration. The penetration of the subchondral layer allows for migration of undifferentiated marrow stem cells that produce type I collagen and subsequently fibrocartilage, but fibrocartilage has poor wear characteristics, limited resilience, increased stiffness and does not slow the progression of osteoarthritis.
Strain-time curve with constant compressive load
Creep deformation
Exudation stops
Equilibrium deformation Rapid fluid exudation
Osteoarthritis
Time
Osteoarthrosis (OA) is one of the most common disorders of the musculoskeletal system, characterised by the destruction of articular cartilage. The joint becomes stiff, swollen, painful and, eventually, deformed. X-rays reveal loss of joint space, subchondral cysts with sclerosis, and osteophytes (see Figures 4 and 5). On inspection, the cartilage may show areas of softening, fibrillation, fissures or gross erosion. There may be areas of full thickness cartilage loss with the subchondral bone exposed, which is often found to be sclerotic. Microscopic appearances include surface irregularities and erosions, deterioration of the tidemark, fissuring and damage to the cartilage structure. Water content is increased in OA, with a decrease in the proteoglycan content. The proteoglycan chain is shorter and the chondroitin/ keratin sulphate ratio is increased. Overall, the collagen content is maintained but the presence of collagenase disrupts its organization and orientation.
Figure 3 Creep-time graph of articular cartilage.
surfaces do not touch and the amount of friction depends on the viscosity of the fluid and the shape of the gap between the two surfaces. In squeeze-film lubrication the two surfaces are apposed without any sliding movement and the joint surfaces are in parallel alignment. The high viscosity of the fluid does not allow the fluid to be squeezed out of the gap between the two surfaces, with a resultant build up in pressure capable of supporting relatively large loads. However, if the large loads are maintained over long periods, the lubricating fluid becomes depleted and the surfaces come into contact. Elastohydrodynamic lubrication is similar to squeeze film lubrication, but in synovial joints the relative velocity of the two opposing surfaces is generally too low to maintain the minimum fluid thickness to ensure absolute separation. The articular surface undergoes transient elastic deformation and presents a larger surface area, thereby allowing for better load tolerance over time (reduction in required relative velocity) due to less dissipation of the fluid-film.
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Specific conditions Osteoarthrosis Management of knee pain and osteoarthritis in the older, less active patient provides a relatively straight forward decision-
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and the talus are also commonly affected. Risk factors include male gender, AfricaneAmerican ethnicity and sports participation. The exact mechanism is yet to be conclusively elucidated, but is thought to be hereditary, traumatic or vascular, with the adult presentation theorised to be vascular in origin.2,3 The process starts with an intact articular surface and the overlying articular cartilage softening, progressing to cartilage separation and then partial detachment of the lesion. Eventually, osteochondral separation is identified and loose bodies are seen on imaging. Presentation at a younger age usually indicates a more optimistic prognosis, with patellar and posterolateral femoral lesions attracting a more pessimistic outlook. Patients normally present with a painful knee, stiffness and recurrent joint effusions. Magnetic resonance imaging is important for assessment of the size of the lesion and the quality of the surrounding articular elements and subchondral bone, and also helps to identify the presence of any loose bodies. Multiple classifications exist for osteochondritis of the knee; however, there is a lack of consistency and there are wide variations. The concept of stability of OCD centres around the mechanical integrity of the lesion.4 Despite the variation in classification systems, there is broad agreement that the initial stages demonstrate softening of the site when probed whereas the articular cartilage remains intact. The intermediate stages reveal fissuring or partial disruption in cartilage that remains stable, and the final stage involves a partially detached fragment progressing through to a loose body within the joint.5,6
Figure 4 End-stage osteoarthrosis of the knee e AP view.
Joint injections Hyaluronic acid (HA) is a macromolecule found naturally within cartilage, with reduced levels in areas where osteoarthritis is present, and it has been studied extensively.7e9 HA has a well documented role in joint lubrication, and viscosupplementation with HA injection into degenerative joints has been shown to improve function and to provide good pain relief in knees,10 with a growing evidence base showing its efficacy in hips, ankles, spine, foot and hand.11,12 Studies comparing corticosteroid injection compared to HA injections have demonstrated that corticosteroid provides rapid relief with a reduction in inflammatory symptoms. HA appears to have a slower effect but results in better functional outcomes that may persist for as long as 6 months post-injection.13,14 Platelet-rich plasma remains a controversial treatment. Its efficacy compared to other more mainstream therapies remains under scrutiny. It is a relatively low cost means of harvesting concentrated autologous growth factors from a blood sample, and by injecting these directly into the affected joint it is proposed that there would be a reduction in pain symptoms and possibly an element of regeneration, secondary to the presence of these bioactive molecules. Results for patients under 50 years of age with very little degeneration demonstrate an improvement in both pain and function, but with more advanced osteoarthritis and with patients over the age of 50 years, results seem to be equivalent to hyaluronic acid at 2 and 6 months post-treatment.15
Figure 5 End-stage osteoarthrosis of the knee e lateral view.
making process. Appropriate management of articular cartilage pathology in younger patients, however, remains a challenge. Options include conservative measures such as targeted physiotherapy, regular oral or topical analgesia/anti-inflammatories, intra-articular injections (corticosteroid or hyaluronic acid) and activity modification. Potential surgical options include microfracture, mosaicplasty, chondrocyte transplant, high tibial osteotomy and unicondylar knee replacement. Total knee replacement can offer a long-term solution, but this needs to be balanced with the physical demand estimation and the potential longevity of the prosthesis. Osteochondritis dissecans Osteochondritis dissecans (OCD) is a focal idiopathic condition of subchondral bone that creates an environment of potential instability and articular cartilage disruption, which may cause premature joint degeneration.1 The most common location is the knee (Figures 6 and 7), with the posterolateral aspect of medial femoral condyle having the greatest incidence. The capitellum
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Surgical treatments for cartilage regeneration Microfracture was developed by Steadman in the 1980s16 as a single-stage arthroscopic technique. The cartilage defect is
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Figure 6 Anteroposterior knee radiograph of the knee of a 15-year-old, showing osteochondritis dissecans of the distal femoral epiphysis with areas of evident epiphyseal necrosis (arrows). Kindly reproduced under open access licence from Al Kaissi A, Klaushofer K, Grill F. Osteochondritis dissecans and Osgood Schlatter disease in a family with Stickler syndrome. Pediatr Rheumatol Online J 2009;7:4.
Figure 8 Arthroscopic view of microfracture. Kindly reproduced under open access licence from Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 2012;94(6):381e387.
carefully debrided back to a healthy stable border and an awl is used to repetitively perforate the subchondral bone (Figure 8), which allows migration of the marrow cells to the surface and creates a clot within the defect, which eventually matures into fibrocartilage. A review of the literature on microfracture reveals good short-term clinical outcomes in low demand patients, but treatment failure after 5 years can be expected regardless of the size of the lesion. Younger patients on average do better postoperatively, regardless of the lesion size.17 Osteochondral autologous transplantation mosaicplasty involves open or arthroscopic implantation of an osteochondral graft from the periphery of a lesser weight-bearing surface of the joint to the defect, which provides a hyaline cartilage resurfacing
solution (Figure 9). Long-term follow-up results show equivalent results between microfracture and mosaicplasty with regards patient outcomes, muscle strength and radiological appearances, but when compared to a healthy population, outcomes in both groups are inferior.18 Autologous chondrocyte implantation (Figure 10) has become more mainstream and has the ability to create a hyaline or hyaline-like repair.19 From a surgical aspect, this technique is advantageous in that there is the possibility of treating large defects with no donor site morbidity and without the need for allograft material. However, the liquid chondrocyte culture medium is fragile, creating the periosteal suture can prove challenging and unless the transplant can be delivered
Figure 7 Coronal T1 weighted magnetic resonance imaging of the knee showing an area of osteochondritis dissecans affecting the medial femoral condyle (a and b). Kindly reproduced under open access licence from Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 2012;94(6):381-7.
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arthroscopically, open surgery may still be required. Third generation techniques have developed HA scaffolds that provide a framework for the cultured cells, to allow cell clusters to form and the extracellular matrix to be deposited, and arthroscopic techniques have been developed but still remain technically challenging and operator dependent. Implant stability and transplanted chondrocyte longevity continue to be a concern, although more recent studies are promising.19e21
Summary Cartilage has a unique structure and function within the human body. Different types of cartilage demonstrate different characteristics and properties, best suited to its specific function. The degenerative process remains a challenge for healthcare professionals, and although research in this area is progressing, successful long-term treatments are still awaited. A REFERENCES 1 Edmonds EW, Shea KG. Osteochondritis dissecans: editorial comment. Clin Orthop Relat Res 2013; 471: 1105e6. 2 Cahill BR. Osteochondritis dissecans of the knee: treatment of Juvenile and adult forms. J Am Acad Orthop Surg 1995; 3: 237e47. 3 Kessler JI, Nikizad H, Shea KG, et al. The demographics and epidemiology of osteochondritis dissecans of the knee in children and adolescents. Am J Sports Med 2014; 42: 320e6. 4 Mesgarzadeh M, Sapega AA, Bonakdarpour A, et al. Osteochondritis dissecans: analysis of mechanical stability with radiography, scintigraphy, and MR imaging. Radiology 1987; 165: 775e80. 5 Chen CH, Liu YS, Chou PH, et al. MR grading system of osteochondritis dissecans lesions: comparison with arthroscopy. Eur J Radiol 2013; 82: 518e25. 6 Hughes JA, Cook JV, Churchill MA, et al. Juvenile osteochondritis dissecans: a 5-year review of the natural history using clinical and MRI evaluation. Pediatr Radiol 2003; 33: 410e7. 7 Ghosh P, Guidolin D. Potential mechanism of action of intraarticular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin Arthritis Rheum 2002; 32: 10e37. 8 Marshall KW. Intra-articular hyaluronan therapy. Curr Opin Rheumatol 2000; 12: 468e74. 9 Kawano T, Miura H, Mawatari T, et al. Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis. Arthritis Rheum 2003; 48: 1923e9. 10 Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum 2009; 61: 1704e11. 11 Kelly MA, Moskowitz RW, Lieberman JR. Hyaluronan therapy: looking toward the future. Am J Orthop (Belle Mead NJ) 2004; 33(suppl 2): 23e8. 12 Altman RD. Status of hyaluronan supplementation therapy in osteoarthritis. Curr Rheumatol Rep 2003; 5: 7e14. 13 Cianflocco AJ. Viscosupplementation in patients with osteoarthritis of the knee. Postgrad Med 2013; 125: 97e105. 14 Monfort J, Rotes-Sala D, Segales N, et al. Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in
Figure 9 Mosaicplasty for an osteocartilaginous fracture of the patella. Kindly reproduced under open access licence from Rastogi A, Srivastava P, Iqbal Z, et al. Role of autologous chondrocyte transplantation in articular cartilage defects: An experimental study. Indian J Orthop 2013;47(2):129e134.
Figure 10 Autologous chondrocyte implantation on a medial femoral condyle, demonstrating the injection of chondrocytes in suspension under a collagen type I/III membrane. The extent of the filling can be seen by the ‘tidemark’ on the membrane, produced by the liquid suspension. Kindly reproduced under open access licence from Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 2012;94(6):381e387.
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osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study. Joint Bone Spine 2015; 82: 116e21. 15 Kon E, Mandelbaum B, Buda R, et al. Platelet-rich plasma intraarticular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 2011; 27: 1490e501. 16 Blevins FT, Steadman JR, Rodrigo JJ, et al. Treatment of articular cartilage defects in athletes: an analysis of functional outcome and lesion appearance. Orthopedics 1998; 21: 761e7. discussion 67e8. 17 Goyal D, Keyhani S, Lee EH, et al. Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy 2013; 29: 1579e88.
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18 Ulstein S, Aroen A, Rotterud JH, et al. Microfracture technique versus osteochondral autologous transplantation mosaicplasty in patients with articular chondral lesions of the knee: a prospective randomized trial with long-term follow-up. Knee Surg Sports Traumatol Arthrosc 2014; 22: 1207e15. 19 Rastogi A, Srivastava P, Iqbal Z, et al. Role of autologous chondrocyte transplantation in articular cartilage defects: an experimental study. Indian J Orthop 2013; 47: 129e34. 20 Marcacci M, Zaffagnini S, Kon E, et al. Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 2002; 10: 154e9. 21 Nazem K, Safdarian A, Fesharaki M, et al. Treatment of full thickness cartilage defects in human knees with autologous chondrocyte transplantation. J Res Med Sci 2011; 16: 855e61.
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Articular cartilage
hyaline cartilage and the chondrocytes are evenly distributed in lacunae. Hyaline cartilage provides the surface coverage of articular surfaces and is also found in the tip of the nose. Elastic cartilage is more opaque and has a yellowish appearance. It is identified microscopically by clearly visible darkstaining elastic fibres embedded in ground substance and it is the presence of these fibres that is the most reliable means for differentiating elastic from hyaline cartilage. Perichondrium is also typically found around elastic cartilage. It is more elastic than other cartilage types and can be found in the epiglottis and external ear, where elasticity of tissues is essential. Fibrocartilage contains fine collagen fibres arranged in layered arrays. Compared to the regimented appearance of hyaline cartilage, fibrocartilage appears more disorganized, with gaps between the lacunae and collagen fibre bundles. It is this open, more flexible structure that makes fibrocartilage a good shockabsorbing material, a property required for the pubic symphysis and intervertebral discs. Fibrous cartilage in the pubic symphysis has a tighter construction, reminiscent of a dense connective tissue with lacunae, whereas the structure of the intervertebral discs is more open. Fibrocartilage is also found in the menisci of the knee.
Deborah Lees Paul Partington
Abstract Cartilage is a resilient structure that is both strong and flexible, and is found in many parts of the body. The type of collagen present in the structure determines the type and properties of the cartilage. The structure of articular cartilage is important for loading responses and lubrication, and a typical curve can be demonstrated for both stressstrain and creep-time properties. Osteoarthritis is a common posttraumatic consequence of articular cartilage injury as well as a wellknown consequence of the ageing process. Different approaches to managing cartilage loss or injury have been explored and include steroid and hyaluronic injections, chondroplasty and chondrocyte transfer, with varying success.
Keywords articular; cartilage; chondrocyte; collagen
Introduction Structure and characteristics of articular cartilage
Cartilage is found in many structures throughout the body and negotiates the balance between the need for structural support and flexibility in a unique fashion. It takes on different forms depending on the particular demand of the structure, and whilst the basic components of extracellular matrix and cells remain consistent, the proportions of these components vary within the cartilage subtypes. Cartilage is formed by chondroblasts, which are mesenchymal in origin and which later mature into chondrocytes. Chondroblasts are thus typically found under the perichondrium along the border of the cartilage plates where new appositional growth occurs, although cartilage can also expand via interstitial growth. In epiphyseal plates, chondrocytes enlarge and divide during maturation to form single or multicellular lacunae arranged in linear stacks. There are five recognized types of cartilage (with typical locations in brackets): hyaline (articular), fibroelastic (meniscus), fibrocartilage (bony insertion of tendon/ligament), elastic (trachea) and physeal cartilage (physis). Healthy hyaline cartilage has a smooth, uniform, glassy appearance and is bluish-white in colour, but may loose some of these characteristics with age. The optical density of the collagen fibres approximates that of the extracellular matrix and they are therefore difficult to differentiate under light microscopy as structures separate from the matrix. Perichondrium covers
Articular cartilage demonstrates both a fluid and a solid phase, which determines its mechanical properties. The fluid phase consists of water and electrolytes and fills the gaps between the solid matrix. This fluid accounts for the majority of the wet weight of articular cartilage. The solid phase contains chondrocytes and an extracellular matrix consisting of proteoglycans, collagen fibres and non-collagenous protein. Type II collagen accounts for 90e95% of the collagen content, with the remainder made up of a variety of other collagen types. The chondrocytes make up the cellular component and they produce and maintain the extracellular matrix. Proteoglycans account for approximately 10e15% of the cartilage structure and function to attract water, thereby improving the overall compressive strength. Proteoglycans are predominantly protein-based molecules, mostly concentrated in the middle layer and less concentrated in the deeper layers. They are made up of repeating disaccharide units (glycosaminoglycans), which are of two main types: chondroitin sulphate and keratin sulphate. Attached carboxyl and sulphate groups give the glycosaminoglycans (GAGs) a high negative charge and as a result they attract cations and water, thereby increasing the osmotic pressure of the structure. GAGs combine with a protein core to form a proteoglycan aggrecan molecule (hydrophilic), which in turn binds to hyaluronic acid (HA) to form a proteoglycan aggregate (macromolecule), and the bond is stabilized by a link protein. The proteoglycans weave between the collagen fibres to create a solid lattice with the ability to control water movement within the structure. Water accounts for 65e80% of the articular cartilage mass, with the highest proportion being near the surface. The high water content of articular cartilage provides incompressibility properties, and when combined with its characteristic structural organization this facilitates its stress-shielding properties. The water content reduces with ageing, leading to increased permeability, reduced strength and a reduced Young’s modulus
Deborah Lees M.Tech(Chiropractic) MBBS MRCS Trauma & Orthopaedic Surgery Specialty Trainee, Northumbria Healthcare NHS Foundation Trust, Orthopaedic Department, Wansbeck General Hospital, Ashington, UK. Paul Partington FRCS FRCS (Trauma & Orthopaedics) Trauma & Orthopaedic Surgery Consultant, Northumbria Healthcare NHS Foundation Trust, Orthopaedic Department, Wansbeck General Hospital, Ashington, UK.
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of elasticity. Ageing also results in increases in chondrocyte size, protein content, stiffness and keratin sulphate to chondroitin sulphate ratio, in combination with a decrease in absolute cell number and proteoglycan size. As the ageing process progresses, type X collagen is expressed, alkaline phosphatase is produced, matrix vesicles develop and matrix calcification is subsequently seen on radiographs as subchondral sclerosis. Degradative enzymes (matrix metaloproteinases) maintain turnover of the matrix by degradation of the proteoglycan aggregates and collagen. Tissue-induced metalloproteinase inhibitors (TIMPs) regulate the matrix degradation by binding to the matrix proteins and also maintain the avascular nature of the cartilage by preventing vascular endothelial migration. Articular cartilage provides a low friction surface that is wear resistant and the layers help to distribute weight in load-bearing joints. Articular cartilage consists of four zones and the tidemark (Figure 1 and Table 1): the zones are characterised on the basis of the chondrocyte shape and the orientation of the Type II collagen.
transforming growth factor beta (TGF-B: proteoglycan synthesis), basic fibroblastic growth factor (b-FGF: DNA synthesis in chondrocytes) and insulin growth factore1 (IGF-1: DNA and cartilage matrix synthesis). Parathyroid hormone and thyroxine stimulate matrix synthesis.
Mechanical properties and stress resistance The mechanical properties of articular cartilage can exhibit great variation as result of its structural complexity and organization. Cartilage is biphasic (fluid and solid phase), visco-elastic in tension (exhibits a stress-strain relationship that is dependent on the load and the rate by which the load is applied) and anisotropic (possesses different mechanical properties depending on the direction of the applied load). Cartilage also undergoes creep (the phenomenon of progressive deformation under constant load) and stress-relaxation (a gradual decrease in stress with time under a constant deformation or strain). These properties are made possible by movement of water and macromolecules within cartilage, as up to 70% of the water content is mobile. Whilst water has the ability to move freely, the macromolecules produce a frictional drag under high load, which restricts the flow of water and stiffens the cartilage structure. Due to the arrangement of the collagen fibres, collagen-proteoglycan relationships and cross-links, directional loading can elicit different responses depending on the direction. In tension, the structural organization of the components is altered, resulting in increased water permeability and reduced compressive stiffness. When articular cartilage specimens are subject to a constant strain, the tensile stress-strain behaviour is non-linear. The characteristic graph curve results from an initial straightening of the slack fibres along with an increasing number of fibres being recruited. The increasing number of collagen fibrils
Metabolism, nourishment and the role of cartilage specific growth factors Articular cartilage is avascular and relies on the diffusion of nutrients from the synovial fluid at its surface and from the subchondral bone at its deep surface. The metabolic rate is very low, with adenosine triphosphate (ATP) production via the lactic acid pathway. The extracellular matrix adjacent to the cellular elements has a relatively high turnover when compared to proteoglycans (weeks to months) and collagen (several years). Various growth factors have been found to play a role in repair, proteoglycan synthesis and chondrocyte DNA synthesis. These include platelet-derived growth factor (PDGF: repair), Chondrocytes
Collagen
Proteogylcans
Zone I Superficial Zone II
Intermediate
Zone III Deep
Tidemark Zone IV Calcified
Subchondral bone
Hydroxyapatite H d crystals t s
Figure 1 Zones of articular cartilage. Zone 1: Flattened chondrocytes, collagen fibres parallel to joint, sparse proteoglycans. Zone II: Round chondrocytes, oblique/random collagen fibres and plentiful proteoglycans. Zone III: Thickest layer, columns of chondrocytes, collagen bundles perpendicular to joint, cross the tidemark and are anchored into subchondral bone, highest proteoglycan content. Zone IV: Type X collagen present and hydroxyapatite crystals anchor cartilage to subchondral bone.
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Summary of the characteristics of the zones of articular cartilage Zone
Cellular components
Collagen components
Proteoglycan components
Additional features
Superficial I (gliding)
Flattened chondrocytes 1e3 layers thick. Exhibit macrophage-type behaviour. Round chondrocytes.
Lamina splendins. Condensed fibres parallel to joint e resists shear stress.
Sparse.
Oblique or random orientation.
Plentiful.
Thinnest layer. Progenitor cells present. May function as a barrier layer regulating molecular movement. Thickest layer. Allows transition from superficial shear to compression stress resistance. Largest part of articular cartilage. Resists compression.
Intermediate II (transitional)
Deep Layer III (radial)
Tidemark
Calcified Zone IV
Round chondrocytes arranged in columns.
Bundles of fibres Highest content anchored into the in all the layers. underlying bone, perpendicular to joint. Crosses tidemark. Only found in joints e cell free layer. Most prominent in mature joints (non-growing). Separates the true articular cartilage from the cartilage anlarge (childhood growth remnant from endochondral ossification). Divides superficial uncalcified layers from deeper calcified layers. Division between chondrocyte nutritional sources. Type X collagen. Hydroxyapatite crystals anchor the cartilage to the subchondral bone.
Subchondral bone Table 1
film formation and efflux of fluid from cartilage. Synovial fluid is essentially an ultra-filtrate of blood plasma. It is a highly viscous, clear, pale yellow liquid secreted by the fibroblast-like type B synovial cells, and mostly consists of hyaluronate (hyaluronic acid) and lubricin (glycoprotein). The volume varies from joint to joint, as does the actual composition. There are two broad categories of lubrication: boundary and fluid-film lubrication, and these theories have been adapted to explain human joint lubrication. Boundary lubrication is most important at rest. When loaded, a thin layer of lubricant fluid prevents direct articular contact. If large loads are maintained for long time periods, the fluid film is depleted except for a layer of lubricant molecules that are chemically attached to the surfaces, thereby creating a boundary layer. This boundary layer has low shear strength and thus offers lower friction than unlubricated surfaces. In synovial joints, lubrican is the lubricating glycoprotein. The lubrican molecules create a monolayer on each articulating surface, which reduces surface friction and prevents articular wear. Hydrodynamic lubrication, squeeze-film lubrication and elastohydrodynamic lubrication are all types of fluid-film lubrication. Hydrodynamic lubrication occurs when the surfaces are at an angle to each other and one surface slides over another with the bearing surface separated by a wedge of fluid. As the surfaces slide over one another, a layer of fluid is dragged through a narrowing wedge-shaped gap. The action creates a hydrodynamic pressure in the fluid, creating a lift force that keeps the sliding surfaces separated. The fluid film ensures the two sliding
resisting the tension force, as the slack fibrils are first straightened and then stretched with the increasing strain, causes the typical curve shape. The characteristic curve (Figure 2) can be separated into two regions: 1) the toe region and 2) the linear region. The toe region is where the coiled collagen fibrils are becoming straightened and are beginning to resist the applied strain. The linear region is where all the collagen fibrils are stretched and are all resisting strain. Creep deformation (Figure 3) occurs as fluid is forced from the tissue during loading. Initially, there is rapid deformation and fluid is rapidly exuded, and flow gradually slows as the remaining amount of fluid diminishes, so the rate of exudation slows until equilibrium is achieved and the fluid flow stops. Physiological stress inhibits chondrolysis and stimulates matrix synthesis, whereas excessive stress promotes chondrolysis and inhibits matrix synthesis. Primary cilia present on chondrocytes and osteoblasts act as a mechanosensory system, with integrin aiding in the transduction of mechanical signals. Immobilization results in cartilage softening, proteoglycan loss and overall reduction of the cartilage thickness. Repetitive loading results in an initial increase in cartilage thickness and proteoglycan content, but once this progresses to strenuous loading, the cartilage starts to thin and the proteoglycan content decreases.
Lubrication and wear One of the functions of articular cartilage is joint lubrication. Cartilage has an extremely low co-efficient of friction, which can be further reduced by elastic deformation, synovial fluid, fluid-
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In reality, however, none of the lubricating mechanisms can individually explain joint lubrication, and synovial joints demonstrate aspects of both boundary and fluid-film lubrication. The prominent mechanism at any single moment is dependent on the current conditions. During range of movement, at the areas that are in close contact, boundary lubrication is characteristic, with fluid-film lubrication seen throughout the remainder of the bearing surface. Boundary and elastohydrodynamic lubrication occur during movement, and a further two types of lubrication (weeping/self-lubrication and boosted lubrication) are thought to occur. In weeping lubrication, fluid is driven both under and in front of the loading surface until maximum compression load is reached, and as the load is lifted the cartilage reforms as the water is re-absorbed. Boosted lubrication involves separation of the lubricating fluid, where the water is driven into the superficial cartilage layers, with concentrated hyaluronic acid remaining on the joint surface. These puddles are described as pools of fluid trapped by contacting areas of the bearing surfaces.
Lin e
ar
Tensile Stress
re g
ion
Stress-strain curve for articular cartilage using a constant strain rate
Toe
on
regi
Strain Figure 2 Stress-strain graph of articular cartilage.
Healing process Articular cartilage has slow growth potential and very poor regenerative capacity due to the lack of direct blood supply; hence the high incidence of post-traumatic degeneration, ageing and condition-specific pathology. Cartilage lacerations superficial to the tidemark do not heal due to the avascular nature of the structure, despite local proliferation of chondrocytes. Lacerations that penetrate deep to the tidemark are able to elicit a healing response via haematoma, endothelial ingrowth and marrow mesenchymal cell migration. The penetration of the subchondral layer allows for migration of undifferentiated marrow stem cells that produce type I collagen and subsequently fibrocartilage, but fibrocartilage has poor wear characteristics, limited resilience, increased stiffness and does not slow the progression of osteoarthritis.
Strain-time curve with constant compressive load
Creep deformation
Exudation stops
Equilibrium deformation Rapid fluid exudation
Osteoarthritis
Time
Osteoarthrosis (OA) is one of the most common disorders of the musculoskeletal system, characterised by the destruction of articular cartilage. The joint becomes stiff, swollen, painful and, eventually, deformed. X-rays reveal loss of joint space, subchondral cysts with sclerosis, and osteophytes (see Figures 4 and 5). On inspection, the cartilage may show areas of softening, fibrillation, fissures or gross erosion. There may be areas of full thickness cartilage loss with the subchondral bone exposed, which is often found to be sclerotic. Microscopic appearances include surface irregularities and erosions, deterioration of the tidemark, fissuring and damage to the cartilage structure. Water content is increased in OA, with a decrease in the proteoglycan content. The proteoglycan chain is shorter and the chondroitin/ keratin sulphate ratio is increased. Overall, the collagen content is maintained but the presence of collagenase disrupts its organization and orientation.
Figure 3 Creep-time graph of articular cartilage.
surfaces do not touch and the amount of friction depends on the viscosity of the fluid and the shape of the gap between the two surfaces. In squeeze-film lubrication the two surfaces are apposed without any sliding movement and the joint surfaces are in parallel alignment. The high viscosity of the fluid does not allow the fluid to be squeezed out of the gap between the two surfaces, with a resultant build up in pressure capable of supporting relatively large loads. However, if the large loads are maintained over long periods, the lubricating fluid becomes depleted and the surfaces come into contact. Elastohydrodynamic lubrication is similar to squeeze film lubrication, but in synovial joints the relative velocity of the two opposing surfaces is generally too low to maintain the minimum fluid thickness to ensure absolute separation. The articular surface undergoes transient elastic deformation and presents a larger surface area, thereby allowing for better load tolerance over time (reduction in required relative velocity) due to less dissipation of the fluid-film.
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Specific conditions Osteoarthrosis Management of knee pain and osteoarthritis in the older, less active patient provides a relatively straight forward decision-
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and the talus are also commonly affected. Risk factors include male gender, AfricaneAmerican ethnicity and sports participation. The exact mechanism is yet to be conclusively elucidated, but is thought to be hereditary, traumatic or vascular, with the adult presentation theorised to be vascular in origin.2,3 The process starts with an intact articular surface and the overlying articular cartilage softening, progressing to cartilage separation and then partial detachment of the lesion. Eventually, osteochondral separation is identified and loose bodies are seen on imaging. Presentation at a younger age usually indicates a more optimistic prognosis, with patellar and posterolateral femoral lesions attracting a more pessimistic outlook. Patients normally present with a painful knee, stiffness and recurrent joint effusions. Magnetic resonance imaging is important for assessment of the size of the lesion and the quality of the surrounding articular elements and subchondral bone, and also helps to identify the presence of any loose bodies. Multiple classifications exist for osteochondritis of the knee; however, there is a lack of consistency and there are wide variations. The concept of stability of OCD centres around the mechanical integrity of the lesion.4 Despite the variation in classification systems, there is broad agreement that the initial stages demonstrate softening of the site when probed whereas the articular cartilage remains intact. The intermediate stages reveal fissuring or partial disruption in cartilage that remains stable, and the final stage involves a partially detached fragment progressing through to a loose body within the joint.5,6
Figure 4 End-stage osteoarthrosis of the knee e AP view.
Joint injections Hyaluronic acid (HA) is a macromolecule found naturally within cartilage, with reduced levels in areas where osteoarthritis is present, and it has been studied extensively.7e9 HA has a well documented role in joint lubrication, and viscosupplementation with HA injection into degenerative joints has been shown to improve function and to provide good pain relief in knees,10 with a growing evidence base showing its efficacy in hips, ankles, spine, foot and hand.11,12 Studies comparing corticosteroid injection compared to HA injections have demonstrated that corticosteroid provides rapid relief with a reduction in inflammatory symptoms. HA appears to have a slower effect but results in better functional outcomes that may persist for as long as 6 months post-injection.13,14 Platelet-rich plasma remains a controversial treatment. Its efficacy compared to other more mainstream therapies remains under scrutiny. It is a relatively low cost means of harvesting concentrated autologous growth factors from a blood sample, and by injecting these directly into the affected joint it is proposed that there would be a reduction in pain symptoms and possibly an element of regeneration, secondary to the presence of these bioactive molecules. Results for patients under 50 years of age with very little degeneration demonstrate an improvement in both pain and function, but with more advanced osteoarthritis and with patients over the age of 50 years, results seem to be equivalent to hyaluronic acid at 2 and 6 months post-treatment.15
Figure 5 End-stage osteoarthrosis of the knee e lateral view.
making process. Appropriate management of articular cartilage pathology in younger patients, however, remains a challenge. Options include conservative measures such as targeted physiotherapy, regular oral or topical analgesia/anti-inflammatories, intra-articular injections (corticosteroid or hyaluronic acid) and activity modification. Potential surgical options include microfracture, mosaicplasty, chondrocyte transplant, high tibial osteotomy and unicondylar knee replacement. Total knee replacement can offer a long-term solution, but this needs to be balanced with the physical demand estimation and the potential longevity of the prosthesis. Osteochondritis dissecans Osteochondritis dissecans (OCD) is a focal idiopathic condition of subchondral bone that creates an environment of potential instability and articular cartilage disruption, which may cause premature joint degeneration.1 The most common location is the knee (Figures 6 and 7), with the posterolateral aspect of medial femoral condyle having the greatest incidence. The capitellum
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Surgical treatments for cartilage regeneration Microfracture was developed by Steadman in the 1980s16 as a single-stage arthroscopic technique. The cartilage defect is
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Figure 6 Anteroposterior knee radiograph of the knee of a 15-year-old, showing osteochondritis dissecans of the distal femoral epiphysis with areas of evident epiphyseal necrosis (arrows). Kindly reproduced under open access licence from Al Kaissi A, Klaushofer K, Grill F. Osteochondritis dissecans and Osgood Schlatter disease in a family with Stickler syndrome. Pediatr Rheumatol Online J 2009;7:4.
Figure 8 Arthroscopic view of microfracture. Kindly reproduced under open access licence from Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 2012;94(6):381e387.
carefully debrided back to a healthy stable border and an awl is used to repetitively perforate the subchondral bone (Figure 8), which allows migration of the marrow cells to the surface and creates a clot within the defect, which eventually matures into fibrocartilage. A review of the literature on microfracture reveals good short-term clinical outcomes in low demand patients, but treatment failure after 5 years can be expected regardless of the size of the lesion. Younger patients on average do better postoperatively, regardless of the lesion size.17 Osteochondral autologous transplantation mosaicplasty involves open or arthroscopic implantation of an osteochondral graft from the periphery of a lesser weight-bearing surface of the joint to the defect, which provides a hyaline cartilage resurfacing
solution (Figure 9). Long-term follow-up results show equivalent results between microfracture and mosaicplasty with regards patient outcomes, muscle strength and radiological appearances, but when compared to a healthy population, outcomes in both groups are inferior.18 Autologous chondrocyte implantation (Figure 10) has become more mainstream and has the ability to create a hyaline or hyaline-like repair.19 From a surgical aspect, this technique is advantageous in that there is the possibility of treating large defects with no donor site morbidity and without the need for allograft material. However, the liquid chondrocyte culture medium is fragile, creating the periosteal suture can prove challenging and unless the transplant can be delivered
Figure 7 Coronal T1 weighted magnetic resonance imaging of the knee showing an area of osteochondritis dissecans affecting the medial femoral condyle (a and b). Kindly reproduced under open access licence from Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 2012;94(6):381-7.
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arthroscopically, open surgery may still be required. Third generation techniques have developed HA scaffolds that provide a framework for the cultured cells, to allow cell clusters to form and the extracellular matrix to be deposited, and arthroscopic techniques have been developed but still remain technically challenging and operator dependent. Implant stability and transplanted chondrocyte longevity continue to be a concern, although more recent studies are promising.19e21
Summary Cartilage has a unique structure and function within the human body. Different types of cartilage demonstrate different characteristics and properties, best suited to its specific function. The degenerative process remains a challenge for healthcare professionals, and although research in this area is progressing, successful long-term treatments are still awaited. A REFERENCES 1 Edmonds EW, Shea KG. Osteochondritis dissecans: editorial comment. Clin Orthop Relat Res 2013; 471: 1105e6. 2 Cahill BR. Osteochondritis dissecans of the knee: treatment of Juvenile and adult forms. J Am Acad Orthop Surg 1995; 3: 237e47. 3 Kessler JI, Nikizad H, Shea KG, et al. The demographics and epidemiology of osteochondritis dissecans of the knee in children and adolescents. Am J Sports Med 2014; 42: 320e6. 4 Mesgarzadeh M, Sapega AA, Bonakdarpour A, et al. Osteochondritis dissecans: analysis of mechanical stability with radiography, scintigraphy, and MR imaging. Radiology 1987; 165: 775e80. 5 Chen CH, Liu YS, Chou PH, et al. MR grading system of osteochondritis dissecans lesions: comparison with arthroscopy. Eur J Radiol 2013; 82: 518e25. 6 Hughes JA, Cook JV, Churchill MA, et al. Juvenile osteochondritis dissecans: a 5-year review of the natural history using clinical and MRI evaluation. Pediatr Radiol 2003; 33: 410e7. 7 Ghosh P, Guidolin D. Potential mechanism of action of intraarticular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin Arthritis Rheum 2002; 32: 10e37. 8 Marshall KW. Intra-articular hyaluronan therapy. Curr Opin Rheumatol 2000; 12: 468e74. 9 Kawano T, Miura H, Mawatari T, et al. Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental osteoarthritis. Arthritis Rheum 2003; 48: 1923e9. 10 Bannuru RR, Natov NS, Obadan IE, et al. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthritis Rheum 2009; 61: 1704e11. 11 Kelly MA, Moskowitz RW, Lieberman JR. Hyaluronan therapy: looking toward the future. Am J Orthop (Belle Mead NJ) 2004; 33(suppl 2): 23e8. 12 Altman RD. Status of hyaluronan supplementation therapy in osteoarthritis. Curr Rheumatol Rep 2003; 5: 7e14. 13 Cianflocco AJ. Viscosupplementation in patients with osteoarthritis of the knee. Postgrad Med 2013; 125: 97e105. 14 Monfort J, Rotes-Sala D, Segales N, et al. Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in
Figure 9 Mosaicplasty for an osteocartilaginous fracture of the patella. Kindly reproduced under open access licence from Rastogi A, Srivastava P, Iqbal Z, et al. Role of autologous chondrocyte transplantation in articular cartilage defects: An experimental study. Indian J Orthop 2013;47(2):129e134.
Figure 10 Autologous chondrocyte implantation on a medial femoral condyle, demonstrating the injection of chondrocytes in suspension under a collagen type I/III membrane. The extent of the filling can be seen by the ‘tidemark’ on the membrane, produced by the liquid suspension. Kindly reproduced under open access licence from Perera JR, Gikas PD, Bentley G. The present state of treatments for articular cartilage defects in the knee. Ann R Coll Surg Engl 2012;94(6):381e387.
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osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study. Joint Bone Spine 2015; 82: 116e21. 15 Kon E, Mandelbaum B, Buda R, et al. Platelet-rich plasma intraarticular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 2011; 27: 1490e501. 16 Blevins FT, Steadman JR, Rodrigo JJ, et al. Treatment of articular cartilage defects in athletes: an analysis of functional outcome and lesion appearance. Orthopedics 1998; 21: 761e7. discussion 67e8. 17 Goyal D, Keyhani S, Lee EH, et al. Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy 2013; 29: 1579e88.
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18 Ulstein S, Aroen A, Rotterud JH, et al. Microfracture technique versus osteochondral autologous transplantation mosaicplasty in patients with articular chondral lesions of the knee: a prospective randomized trial with long-term follow-up. Knee Surg Sports Traumatol Arthrosc 2014; 22: 1207e15. 19 Rastogi A, Srivastava P, Iqbal Z, et al. Role of autologous chondrocyte transplantation in articular cartilage defects: an experimental study. Indian J Orthop 2013; 47: 129e34. 20 Marcacci M, Zaffagnini S, Kon E, et al. Arthroscopic autologous chondrocyte transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 2002; 10: 154e9. 21 Nazem K, Safdarian A, Fesharaki M, et al. Treatment of full thickness cartilage defects in human knees with autologous chondrocyte transplantation. J Res Med Sci 2011; 16: 855e61.
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