28-29-30 November 2013
Pieter J. Emans, MD, PhD
Joint motion is possible by a truly remarkable material both structurally and functionally called hyaline cartilage [1-3]. Different types of cartilage can be found in the human body; (i) hyaline, (ii) elastic and (iii) fibro cartilage. Elastic cartilage is found in the ear and respiratory tract. The menisci and intervertebral discs contain fibrocartilage and hyaline cartilage is predominantly found in articulating joints. The chondrocyte is the only cell type found in articular cartilage. In contrast to other tissues, the chondrocyte contributes to a relative low percentage of the cartilage volume (1-5 percent). In adults these chondrocytes lack cell-cell contact. Therefore communication between cells has to occur via the extracellular matrix (ECM). Cartilage is characterized by the absence of blood vessels, lymphatic necessitates and nerve fibres. Chondrocytes receive nutrients and oxygen via diffusion from the synovial fluid through the ECM and from the underlying bone. Their environment is therefore dominated by low oxygen levels and these cells have an anaerobic metabolism . Each chondrocyte is a metabolically active unit which elaborates and maintains the ECM in its immediate vicinity . Cartilage is capable to withstand high mechanical forces combined with a very low friction. These unique mechanical properties are due to the arcade like structure of cartilage and as such four zones are discriminated, based on chondrocyte shape and distribution and collagen type II orientation [1, 2, 6]. In the superficial or tangential zone, chondrocytes are disc shaped and form a layer of several cells thick. The long axes of the cells are parallel to the joint surface and the cells are surrounded by a thin layer of ECM. Thin collagen fibres are oriented parallel with the articular surface. This orientation and the relatively low content of proteoglycans results in high tensile stiffness and the ability to distribute load over the surface. The cells in the transitional or middle zone are more spherical and appear dispersed randomly [7, 8]. Collagen fibers in this zone are organized randomly. At this zone high concentrations of proteoglycans enable the tissue to bear compressive forces. In the radial or deep zone, chondrocytes are ellipsoid, grouped radially in columns of 2-6 cells with their long axes perpendicular to the joint surface. The thicker collagen fibres are also arranged perpendicular to the articular surface. In the calcified zone, chondrocytes are distributed sparsely and remain surrounded by a calcified matrix. The calcified cartilage is less stiff than the subchondral bone. At this calcified zone shear stresses are converted into compressive forces which are in turn transmitted to the subchondral bone . The junction between uncalcified and calcified cartilage is called the “tidemark”, a line which histologically can be seen. Therefore mechanical forces also change at the tidemark which provides a definite boundary for the uncalcified layer [8, 10].
Cartilage defects can be due to trauma or cartilage degeneration. A British surgeon William Hunter made the now famous statement that “From Hippocrates to the present age it is universally allowed that ulcerated cartilage is a troublesome thing and that once destroyed it is not repaired” (Hunter 1743)[11, 12].Although history taking may differentiate between traumatic and degenerative lesions, the exact cause of cartilage defects often remains difficult to diagnose. As mentioned before cartilage lesions remain difficult to treat, whereas the progenitor cells of bone marrow and periosteum contribute to bone formation during fracture healing, articular cartilage is deprived from these progenitors. It has been shown that the superficial layer of cartilage and the synovium contain progenitor cells [13, 14]. Although these progenitor cells are present, in contrast to bone, cartilage has a limited ability for self repair [15, 16]. Damage to the joint surface may lead to premature osteoarthritis [17, 18].
Diagnosis of cartilage defects.Since cartilage has no nerve fibers, cartilage lesions often present with only (minor) effusion of the affected joint or without symptoms. Diagnosis of structures likely to be damaged upon trauma (e.g. subchondral bone, ligaments or menisci), may reveal a cartilage lesion. A X-ray indicates a cartilage lesion in the minority of the cases and Magnetic Resonance Imaging (MRI) is the best non-invasive technique available for diagnosis of cartilage lesions. Important developments are new protocols such as delayed Gardolinium Enhanced MRI of Cartilage (dGEMRIC) and sodium MRI which can visualize cartilage on a Collagen and GAG content level . Overall the MRI is expected to diagnose cartilage lesions in a early stage and will become more important in evaluation of progression of cartilage degeneration and cartilage repair techniques.Articular cartilage lesions which fail to heal spontaneously eventually evolve in osteoarthritis (OA) [15, 18, 20]. OA is among the most frequent forms of musculoskeletal disorders affecting over 10% of the adult population . While primary osteoarthritis (OA) is defined as joint degeneration without any underlying cause, in secondary OA joint degeneration is often caused by trauma (e.g. during sports or in traffic accidents). Traumatic cartilage lesions can be asymptomatic, the percentage of individuals suffering from OA due to a trauma is unknown and may be underestimated. From literature it is known that sixteen to twenty percent of patients with a traumatic hemarthros have a cartilage defect [22, 23], and even up to 60% of patients undergoing a arthroscopy have a cartilage defect [24-26].
Treatment of damaged cartilage. Multiple strategies can be considered when attempts are made to heal or restore cartilage. Subchondral Drilling, Abrasion of Microfracture are techniques to allow penetration of bone marrow through the subchondral bone into the damaged cartilage [27-36]. These techniques improve the clinical well being of the patient and the joint surface defect may be healed to some extend. However the healing process is inadequate since no functional hyaline cartilage but fibrocartilage is formed [28, 36]. However, these methods are cheap and easy to perform and are therefore seen as the best option to do no harm and relieve the complaints. Other clinical studies have suggested that any beneficial effect is related to the arthroscopic procedure itself. A nonspecific effect might be related to joint lavage rather than the penetration of the subchondral bone [37, 38]. In conclusion, these techniques may have some benefit with regard to small defects and no effect has been proved in relation to large defects, osteoarthritic joints or older patients . Implantsvary from non-absorbable and absorbable implants, cells, periosteum or perichondium, Osteochondral Autograft Transfer System (OATS or Mosaicplasty) and Osteochondral Allografts [39-45]. The biomaterials, and periosteum can be combined with cells or growth factors. Periosteal Arthroplastyis an interesting way of treating cartilage defects since many have reported the chondrogenic potential of periosteum [16, 46-57]. More than 90 percent of collagen type II has been reported in the hyaline cartilage formed in the cartilage defects treated with periosteal grafts [47, 48]. The cambium layer should be place so that it faces towards the joint surface (fibrin layer towards the subchondral bone). Perichondrial Arthroplastyused for human cartilage repair was first described by Skoog et al.. This technique has been reported to give an initial cartilage repair [59, 60]. On the long term poor results related to overgrowth of the graft and calcification as reported by Bouwmeester et al.. Osteochondral Graftscan be divided in autogenous and allogeneous. Mosaicplasty or OATS involves harvesting one or more osteochondral plugs from a relatively less weight-bearing region of the joint and subsequent implantation of this graft into an articular defect. Repair of cartilage defects in the knee and talar dome seem to be successful however donor site complications remain a concern. This possible donor site morbidity is bypassed if osteochondral allografts are used [62-70]. This technique is reported to be successful when applied for articular defects of the knee [64, 67, 71]. New approaches for cartilage repair are the co-culture technique which is currently brought to the market by CellCoTec. Using this method both chondrocytes and stemcells are harvested, isolated and a mix of these cells are re-implanted into the defect. The advantage of this technique is that expensive and time consuming culture procedures are bypassed in a one step procedure. Another example is the Cartilage Autograft Implantation System (CAIS) which uses minced cartilage from a relatively unloaded area which is consequently implanted into the defect. First results show CAIS is a safe, feasible, and effective method that may improve long-term clinical outcomes . Early cartilage of callus can also be used for repair of osteochondral defects. Takahashi et al. was the first to report that early fracture callus which was implanted into osteochondral defects of rabbit knees healed with excellent results . Emans et al. repeated these results by transplantation of ectopical cartilage from periosteum[16, 74]. Later periosteal chondrogenesis was induced by subperiosteal injection of a biogel and again transplantation of this cartilage resulted in a superior healing of osteochondral defects compared to empty defects. The main advantage of this approach is that the body is used as its own “in –situ incubator”; cells provide their own matrix, the joint is not further damaged, andcomplex and costly isolation, selection and culturing procedures are bypassed.
Factors influencing cartilage repair have to be considered for understanding the nature of such lesions and comparing and discussing different options for cartilage repair. Depth of the defect is of importance since, in contrast to chondral defects, the underlying vascularized bone is penetrated in osteochondral defects. In osteochondral defects, mesenchymal stem cells and blood cause a limited repair response . After filling with granulation tissue, these injuries undergo repair with fibro-cartilage [75, 76]. Formation of fibrocartilage may relieve symptoms. However, in contrast to hyaline cartilage, fibrocartilage can withstand tension but not repetitive compression forces. In time, this incapacity will lead to degeneration [30, 77]. Chondral defects are partial thickness defects and often fail to heal spontaneously [20, 32]. These lesions usually progress to more widespread degeneration that eventually may lead to osteoarthritis . Specially in these defects, the absence of blood vessels and nerve fibers or the inability of chondrocytes to migrate through the tight ECM may be the underlying cause of this poor regenerative capacity . Anti-adhesiveness of reparative cells of the articular cartilage matrix has also been reported to be the underlying cause . Location of the defect influences and progression of the lesion. Lesions located in the central region of the medial compartment are more likely to progress to advanced cartilage degeneration than lesions located anterior and posterior or lesions located in the lateral compartment. Lesions located in the anterior region of the lateral compartment are the least progressive lesions . Size of the defect correlates with the healing capacity of the defect; the smaller the defect, the larger the chance of healing . Lesions smaller than a “critical size” defect may heal completely. Lesions larger than this “critical size” encounter a limited healing process. The size and definition of a “critical size” defect is different between species. In contrast, Lang et al have described that no specific grade of lesion identified at baseline had a predilection for more rapid cartilage loss .Age of the patient, many clinical studies show that better clinical results are obtained if the patient is younger than 30 years[81, 82]. Body Status of the opposing cartilage is of essence since cartilage defects or abnormalities of this cartilage may negatively influence the healing of the treated defect. As such “kissing” cartilage lesions are a relatively contra-indication for cartilage repair. Time between first complaints/initiation of cartilage defect and treatment influences the outcome. Treatment of “old” defects has an inferior outcome compared to defects treated within 3 years after the diagnosis [82, 83]. Structure and status of the subchondral bone plays an important role. It is therefore also of importance to evaluate the sbchondral bone and based on this evaluation decide which technique of cartilage repair is the method of choice . Prior cartilage treatments which were performed also negatively influence the outcome. In other words, if a defect is treated before the prognosis of the second or even third treatment is inferior. Anterior Cruciate Ligament (ACL) tears and meniscal tears have a negative effect on cartilage healing. In patients who have sustained a meniscus tear, a higher rate of cartilage loss is observed than in those who have intact menisci. Although not significant, ACL tears show a tendency to increase loss of cartilage as well .Weight of the patient and alignment of the leg influence the healing of cartilage. Loading forces of cartilage increase with overweight and malalignment. In these situations cartilage repair is negatively influenced since the mechanical demands for the repaired cartilage are much higher and the repaired cartilage may be damaged upon loading.Continuous passive motion enhances healing of many types of articular cartilage lesions [32, 48, 50, 85-91]. In contrast to immobilization using cast or allowing load bearing, continuous passive motion enhances formation of hyaline cartilage in rabbits . Overall the current role of continuous passive motion is accepted to have a beneficial effect when combined with other strategies aimed at cartilage repair e.g. subchondral penetration, periosteal transplantation etc. [32, 47, 48, 87].
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