Definition and classification of early osteoarthritis of the knee

With the emerging interest in regenerative medicine and tissue engineering, new treatment modalities being developed for joint disorders including joint surface lesions and articular cartilage defects. The clinical outcome of these novel approaches appears rather unpredictable and is due to many reasons but definitely also linked to the patient profile. As a typical example, symptomatic articular cartilage lesions can be presented in an otherwise normal joint, or associated with several other joint tissue alterations including meniscal lesions and abnormalities of the underlying bone. The outcome of novel treatments may well be influenced by the status of the whole joint, and the potential to develop osteoarthritis. To better identify the patients at risk and responders to certain treatments, it is of use to define and most importantly classify patients with “early osteoarthritis”. Here, classification criteria for this group of patients are presented, allowing a more defined and accurate inclusion in clinical trials in the future.     

Advanced morphological and biochemical magnetic resonance imaging of cartilage repair procedures in the knee joint at 3 Tesla

Morphological and biochemical magnetic resonance imaging (MRI) is due to high field MR systems, advanced coil technology, and sophisticated sequence protocols capable of visualizing articular cartilage in vivo with high resolution in clinical applicable scan time. Several conventional two-dimensional (2D) and three-dimensional (3D) approaches show changes in cartilage structure. Furthermore newer isotropic 3D sequences show great promise in improving cartilage imaging and additionally in diagnosing surrounding pathologies within the knee joint. Functional MR approaches are additionally able to provide a specific measure of the composition of cartilage. Cartilage physiology and ultra-structure can be determined, changes in cartilage macromolecules can be detected, and cartilage repair tissue can thus be assessed and potentially differentiated. In cartilage defects and following nonsurgical and surgical cartilage repair, morphological MRI provides the basis for diagnosis and follow-up evaluation, whereas biochemical MRI provides a deeper insight into the composition of cartilage and cartilage repair tissue. A combination of both, together with clinical evaluation, may represent a desirable multimodal approach in the future, also available in routine clinical use.     

Autologe Chondrozytentransplantation zur Behandlung von Knorpeldefekten des Kniegelenks

BACKGROUND: Currently the use of autologous chondrocytes as a cartilage-repair procedure for the repair of injured articular cartilage of the knee joint, is recommended. METHODS: This review presents the technique of autologous chondrocyte transplantation (ACT) and their modifications as matrix-associated autologous chondrocyte transplantation (MACT). Beside the surgical procedure the experimental and clinical results are discussed. Furthermore the major complications and the indication guidelines are presented. RESULTS: Articular cartilage in adults has a poor ability to self-repair after a substantial injury. Surgical therapeutic efforts in treating cartilage defects have focused on bringing new cells capable of chondrogenesis into the lesions. With ACT good to excellent clinical results are seen in isolated posttraumatic lesions of the knee joint in the younger patient with the formation of hyaline-like repair tissue. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. The current limitations include osteoarthritic defects and higher patient age. CONCLUSION: With the right indication and operative technique ACT is an effective and save option for the treatment of large full thickness cartilage defect of the knee joint.     

MR imaging of cartilage repair surgery of the knee

Articular cartilage is a complex tissue with unique properties that are essential for normal joint function. Many processes can result in cartilage injury, ranging from acute trauma to degenerative processes. Articular cartilage lacks vascularity, and therefore most chondral defects do not heal spontaneously and may require surgical repair. A variety of cartilage repair techniques have been developed and include bone marrow stimulation (microfracture), osteochondral autograft transfer system (OATS) or osteochondral allograft transplantation, autologous chondrocyte implantation (ACI), matrix-assisted chondrocyte implantation (MACI), and other newer processed allograft cartilage techniques. Although arthroscopy has long been considered as the gold standard for evaluation of cartilage after cartilage repair, magnetic resonance (MR) imaging is a non-invasive method to assess the repair site and can be scored using Magnetic resonance Observation of Cartilage Repair Tissue (MOCART). MR also provides additional evaluation of the subchondral bone and for other potential causes of knee pain or internal derangement. Conventional MR can be used to evaluate the status of cartilage repair and potential complications. Compositional MR sequences can provide supplementary information about the biochemical contents of the reparative tissue. This article reviews the various types of cartilage repair surgeries and their postoperative MR imaging appearances.     

MR imaging of cartilage repair surgery of the knee

Articular cartilage is a complex tissue with unique properties that are essential for normal joint function. Many processes can result in cartilage injury, ranging from acute trauma to degenerative processes. Articular cartilage lacks vascularity, and therefore most chondral defects do not heal spontaneously and may require surgical repair. A variety of cartilage repair techniques have been developed and include bone marrow stimulation (microfracture), osteochondral autograft transfer system (OATS) or osteochondral allograft transplantation, autologous chondrocyte implantation (ACI), matrix-assisted chondrocyte implantation (MACI), and other newer processed allograft cartilage techniques. Although arthroscopy has long been considered as the gold standard for evaluation of cartilage after cartilage repair, magnetic resonance (MR) imaging is a non-invasive method to assess the repair site and can be scored using Magnetic resonance Observation of Cartilage Repair Tissue (MOCART). MR also provides additional evaluation of the subchondral bone and for other potential causes of knee pain or internal derangement. Conventional MR can be used to evaluate the status of cartilage repair and potential complications. Compositional MR sequences can provide supplementary information about the biochemical contents of the reparative tissue. This article reviews the various types of cartilage repair surgeries and their postoperative MR imaging appearances.     

Effects of calcified cartilage on healing of chondral defects treated with microfracture in horses

BACKGROUND: Microfracture of full-thickness articular defects has been shown to significantly enhance the amount of repair tissue. However, there is a suggestion that leaving calcified cartilage inhibits this repair response. HYPOTHESIS: Removal of the calcified cartilage with retention of subchondral bone enhances the amount of attachment of the repair tissue compared with retention of the calcified cartilage layer. STUDY DESIGN: Controlled laboratory study. METHODS: There were 1-cm(2) articular cartilage defects made in 12 skeletally mature horses on the axial weightbearing portion of both medial femoral condyles. Using a custom measuring device and direct arthroscopic observation of the subchondral bone beneath the calcified cartilage layer, the authors removed the calcified cartilage from 1 defect of each horse. The repair was assessed with arthroscopy, clinical examination, radiographic and magnetic resonance imaging examinations, biopsy at 4 months, gross and histopathologic examinations at 12 months, as well as mRNA and immunohistochemical evaluations. RESULTS: Removal of calcified cartilage with retention of the subchondral bone plate increased the overall repair tissue as assessed by arthroscopic (4 months) and gross evaluation (12 months). An increase in the level of the subchondral bone was also observed with removal of the calcified cartilage layer. The clinical pain, radiographic examinations, magnetic resonance imaging evaluations, histologic character, matrix proteins, or mRNA expression do not appear to differ based on level of defect debridement. CLINICAL RELEVANCE: Removal of the calcified cartilage layer appears to provide optimal amount and attachment of repair tissue. Therefore, close arthroscopic visualization is recommended for debridement of clinical lesions to ensure removal of the calcified cartilage layer.     

Osteochondral allograft transplantation

Experience with fresh osteochondral allografting for cartilage defects in the knee now extends two decades. Clinical outcomes and basic scientific investigations have supported the theoretic basis for this procedure. At the University of California, San Diego, our experience has encouraged us to continue to offer this procedure as a primary treatment for both large and small articular cartilage defects in the young knee. The success rate of fresh osteochondral allografting, particularly in isolated femoral condylar defects, compares favorably with other presently available cartilage repair and resurfacing techniques. In our second hundred cases, which we are currently evaluating, failure of monopolar allografts has been exceedingly rare in short-term follow-up. Fresh osteochondral allografting also appears to be effective in treating larger osteochondral lesions, where there are few other attractive alternatives. Fresh osteochondral allografts can thus be used to treat a wide spectrum of articular pathology. Technical refinements, and improvement in our understanding of graft-host interaction, as well as chondrocyte biology, should continue to improve clinical results. Disadvantages of fresh osteochondral allografting include the relative paucity of donor tissue, complexities in procurement and handling, and the possibility of disease transmission through the transplantation of fresh tissue. At present, only institutions that have overcome these obstacles seem capable of routinely performing this type of articular cartilage transplantation. In the future, as tissue banking and cartilage storage technology advance, fresh allograft tissue may become more available, allowing more widespread use of fresh osteochondral allografting in the treatment of articular cartilage lesions.     

MR imaging of osteochondral grafts and autologous chondrocyte implantation

Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible.     

MR imaging of the postoperative knee: a pictorial essay.

Magnetic resonance (MR) imaging of the postoperative knee has become more common because more arthroscopic repair procedures are being performed. The most common procedures include partial meniscectomy and meniscal repair, anterior cruciate ligament (ACL) reconstruction, and cartilage repair procedures. Specific findings of a retorn meniscus following meniscal repair or partial meniscectomy are increased signal intensity extending through the site of repair on T2-weighted images, displaced meniscal fragments, and abnormal signal intensity at a site distant from the repair. Findings of ACL graft disruption on T2-weighted MR images include absence of intact graft fibers and increased signal intensity similar to that of fluid within the expected region of the graft. Partial tears of the graft appear as areas of increased signal intensity affecting a portion of the graft with some intact fibers still present. An impinged ACL graft may appear to be draped over the anterior inferior edge of the intercondylar roof or be posteriorly bowed. Localized anterior arthrofibrosis appears on T1-weighted MR images as a focal nodular lesion of low signal intensity that is anterior to the ACL graft in the intercondylar notch and is indistinguishable from adjacent joint fluid. On T2-weighted images, the nodule is well differentiated from high-signal-intensity joint fluid. Finally, MR imaging has been shown to be accurate in the evaluation of cartilage repair tissue. Knowledge of the normal MR imaging appearance of the knee after the more common repair procedures will allow radiologists to recognize complications associated with such procedures.     

The use of carbon fiber pads inchondral injury and early osteoarthritis

Articular cartilage damage in young active individuals is a cause of pain and disability and may lead to earlyosteoarthritis. Methods proposed for treatment include intact cartilage grafting, osteochondral grafting, and isolated chondrocyte autografts. However, in some joints it is possible to repair the surface by stimulating the patient's repair mechanisms with techniques such as drilling and abrasion arthroplasty The repair tissue produced by such procedures, however, is usually of inferior quality with regard to the collagen (type I and III) and the proteoglycans. The use of carbon fiber pads as a support for such repair material has proved successful, particularly for the medial femoral condyle of the knee over a period of 5.8 years. The concept of supporting the matrix of the repair material which is formed from the subchondral bone by the use of a carbon fiber matrix is valuable and may be developed by the use of other biodegradable matrices in the future.     

Clinical and MRI considerations in sports-related knee joint cartilage injury and cartilage repair

Cartilage injuries of the knee occur frequently in professional and amateur athletes and can be associated with severe debilitation and morbidity. They are commonly associated with ligament injuries but also may be frequently isolated. Increasing awareness and advances in magnetic resonance imaging (MRI) have led to increasing diagnosis and recognition of these injuries. Articular cartilage is just 2 to 4 mm thick and is avascular, alymphatic, and aneural. It has a limited capacity for healing, and there has been increasing use of cartilage repair techniques to treat these lesions in the active population. Strategies for cartilage repair include marrow stimulation techniques such as microfracture/drilling, osteochondral grafting, and autologous chondrocyte transplants. MRI is an important tool in the diagnosis and grading of cartilage injury and is useful in the follow-up and monitoring of these repair procedures. It is important for radiologists and clinicians to be aware of the capabilities and limitations of MRI in assessing cartilage injury and to be familiar with common postsurgical appearances to facilitate assessment and follow-up in this population. This article reviews the clinical findings and MRI imaging appearances of cartilage injury. The management options are discussed as well as common postsurgical appearances following the various interventions.     

MR Imaging of Postoperative Talar Dome Lesions

The number of surgical interventions of osteochondral lesions in the talar dome is steadily increasing. The surgical treatment with microfracturing or autologous chondrocyte transplantation has shown good clinical outcome at the midterm follow-up. With the development of advanced MR methods that are relatively specific for ultrastructural components of articular cartilage, compositional or biochemical MR has become possible in addition to the standard morphological evaluation of repair tissue. These quantitative MR techniques allow a monitoring of repair tissue on a molecular level. Using these techniques, the maturation of repair tissue, in particular the glycosaminoglycan content responsible for the biomechanical properties and the organization and content of collagen fibers, can be quantified and compared with normal hyaline cartilage. In addition, the diffusion properties of the repair tissue can also be analyzed by specific MR sequences.     

Magnetization transfer contrast and T2 mapping in the evaluation of cartilage repair tissue with 3T MRI

PURPOSE: To use magnetization transfer (MT) imaging in the visualization of healthy articular cartilage and cartilage repair tissue after different cartilage repair procedures, and to assess global as well as zonal values and compare the results to T2-relaxation. MATERIALS AND METHODS: Thirty-four patients (17 after microfracture [MFX] and 17 after matrix-associated autologous cartilage transplantation [MACT]) were examined with 3T MRI. The MT ratio (MTR) was calculated from measurements with and without MT contrast. T2-values were evaluated using a multiecho, spin-echo approach. Global (full thickness of cartilage) and zonal (deep and superficial aspect) region-of-interest assessment of cartilage repair tissue and normal-appearing cartilage was performed. RESULTS: In patients after MFX and MACT, the global MTR of cartilage repair tissue was significantly lower compared to healthy cartilage. In contrast, using T2, cartilage repair tissue showed significantly lower T2 values only after MFX, whereas after MACT, global T2 values were comparable to healthy cartilage. For zonal evaluation, MTR and T2 showed a significant stratification within healthy cartilage, and T2 additionally within cartilage repair tissue after MACT. CONCLUSION: MT imaging is capable and sensitive in the detection of differences between healthy cartilage and areas of cartilage repair and might be an additional tool in biochemical cartilage imaging. For both MTR and T2 mapping, zonal assessment is desirable.     

Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

Purpose

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.

Methods

The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells.

Results

The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration.

Conclusions

Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments.

Level of evidence

IV.     

Cartilage imaging: motivation,techniques, current and future significance

Cartilage repair techniques and pharmacological therapies are currently areas of major clinical interest and research, in particular to prevent and treat osteoarthritis. MR imaging-based techniques to visualize cartilage are prerequisites to guide and monitor these therapies. In this review article, standard MR imaging sequences are described, including proton density-weighted fast spin echo, spoiled gradient echo and dual echo steady state sequences. In addition, new sequences that have been developed and are currently being investigated are presented, including driven equilibrium Fourier transform and steady-state free precession-based imaging. Using high-field MR imaging at 3.0-T, visualization of cartilage and the related pathology has been improved. Volumetric quantitative cartilage MR imaging was developed as a tool to monitor the progression of osteoarthritis and to evaluate new pharmacological cartilage protective therapies. The most exciting developments, however, are in the field of cartilage matrix assessment with quantitative dGEMRIC, T2 and T1rho mapping techniques. These techniques aim at detecting cartilage damage at a stage when changes are potentially still reversible, before cartilage tissue is lost. There is currently substantial interest in these techniques from rheumatologists and orthopedists; radiologists therefore need to keep up with these developments.     

Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration

Purpose

Osteochondral defects (i.e., defects which affect both the articular cartilage and underlying subchondral bone) are often associated with mechanical instability of the joint and therefore with the risk of inducing osteoarthritic degenerative changes. This review addresses the current surgical treatments and most promising tissue engineering approaches for articular cartilage and subchondral bone regeneration.

Methods

The capability to repair osteochondral or bone defects remains a challenging goal for surgeons and researchers. So far, most clinical approaches have been shown to have limited capacity to treat severe lesions. Current surgical repair strategies vary according to the nature and size of the lesion and the preference of the operating surgeon. Tissue engineering has emerged as a promising alternative strategy that essentially develops viable substitutes capable of repairing or regenerating the functions of damaged tissue.

Results

An overview of novel and most promising osteochondroconductive scaffolds, osteochondroinductive signals, osteochondrogenic precursor cells, and scaffold fixation approaches are presented addressing advantages, drawbacks, and future prospectives for osteochondral regenerative medicine.

Conclusion

Tissue engineering has emerged as an excellent approach for the repair and regeneration of damaged tissue, with the potential to circumvent all the limitations of autologous and allogeneic tissue repair.

Level of evidence

Systematic review, Level III.     

MR示踪技术在干细胞移植治疗软骨缺损中的研究进展

关节软骨缺损临床十分常见, 但目前的治疗方法均存在修复不完全的缺陷。间充质干细胞移植治疗的发展为再生修复关节软骨缺损提供了新的治疗策略, 但是作为组织修复执行者的干细胞移植后的在体迁徙分布、增殖及转归过程, 目前尚无安全无创、实时动态的监测手段, 因此难以明确外源性干细胞在关节软骨缺损再生修复中所扮演的角色。而MR在体示踪细胞技术为解决上述问题提供了新思路。MRI具有无创、无电离辐射、时间空间分辨率高、对比度好等优点, 协同MRI对比剂, 既可无创提供关节软骨的详细解剖结构信息, 还可动态评估移植干细胞的归宿。笔者就MR示踪技术在干细胞移植治疗软骨缺损中的最新研究进展进行综述, 探讨其优势、局限性及未来前景。     

MRI of articular cartilage: revisiting current status and future directions

OBJECTIVE: The purpose of this article is to review the current understanding of the MRI appearance of articular cartilage and its relationship to the microscopic and macroscopic structure of articular cartilage, the optimal pulse sequences to be used in imaging, the appearance of both degenerative and traumatic chondral lesions, the appearance of the most common cartilage repair procedures, and future directions and developments in cartilage imaging. CONCLUSION: Articular cartilage plays an essential role in the function of the diarthrodial joints of the body but is frequently the target of degeneration or traumatic injury. The recent development of several surgical procedures that hold the promise of forming repair tissue that is hyaline or hyalinelike cartilage has increased the need for accurate, noninvasive assessment of both native articular cartilage and postoperative repair tissue. MRI is the optimal noninvasive method for assessment of articular cartilage.     

Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: its significance in cartilage repair and replacement

Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.