组织工程软骨移植物修复兔关节软骨缺损

目的　观察组织工程软骨移植物修复兔关节软骨缺损的效果。　方法　经软骨起源诱导后的兔骨髓间质干细胞(mesenchymalstemcells,MSCs),与牛Ⅰ型胶原及人纤维蛋白相混合制成组织工程软骨移植物。60只5个月龄的日本大耳白兔均分为软骨移植物组、单纯载体对照组和空白对照组,观察各组修复兔股骨髁关节软骨全层缺损的效果。　结果　软骨移植物组12周时已形成正常厚度的软骨层及完整的软骨下骨板,O'drilscoll组织学评分18.22±2.45,Ⅱ型胶原含量97.9%,甲苯胺蓝变色反应表明其与周围正常软骨无明显区别,为透明软骨组织修复。而对照组12周时为纤维软骨修复,后期为纤维组织和板层骨修复。　结论　该组织工程软骨移植物作为软骨移植的替代物是可行的。     

Articular cartilage: injury pathways and treatment options

Articular cartilage injury and degeneration is a frequent occurrence in synovial joints. Treatment of these articular cartilage lesions are a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Nonoperative treatments endeavor to control symptoms, and include anti-inflammatory medication, viscosupplementation, bracing, orthotics, and activity modification. Techniques to stimulate the intrinsic repair (fibrocartilage) process include drilling, abrasion, and microfracture of the subchondral bone. Currently, the clinical biologic approaches to treat cartilage defects include autologous chondrocyte implantation, periosteal transfer, and osteochondral autograft or allograft transplantation. Newer strategies employing tissue engineering being studied involve the use of combinations of progenitor cells, bioactive factors, and matrices, and the use of focal synthetic devices. Many new and innovative treatments are being explored in this exciting field. However, there is a paucity of prospective, randomized controlled clinical trials that have compared the various techniques, treatment options, indications and efficacy.     

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.     

A practical guide to imaging of cartilage repair with emphasis on bone marrow changes

Orthopedic surgeons have multiple options available to treat articular cartilage lesions, including microfracture, osteochondral autografting, and autologous chondrocyte implantation. By having basic knowledge of these surgical procedures, radiologists can more accurately interpret imaging studies obtained after surgery. In this article, we briefly review the different types of cartilage repair procedures, their appearance on magnetic resonance imaging (MRI), and pathologic MRI findings associated with postoperative complications. We also briefly discuss advanced MRI techniques (T2 mapping, delayed gadolinium-enhanced MRI of cartilage, sodium MRI) that have been recently used to assess the biochemical composition of repair tissue matrix. MRI can accurately assess the status and health of cartilage repair tissue. By providing this information to orthopedic surgeons, radiologists can play a valuable role in the management of patients who undergo cartilage repair surgery.     

组织工程重建兔颞下颌关节盘软骨

目的 应用组织工程学方法重建颞下颌关节盘软骨。方法 分离6只日本大耳白兔髁状突软骨细胞。进行细胞的微载体大规模扩增,将扩增后的软骨细胞接种于组织引导再生胶原膜,体外适当培养后植入4只同种成年兔皮下,植入后12周,对所获组织进行组织形态学观察。结果 髁状[突软骨细胞在胶原膜内生长良好,植入动物体内12周后可形成乳白色类软骨样组织,其表面光滑,有弹性。甲苯胺蓝染色,细胞周围基质呈异染性。结论 应用胶原膜结合软骨细胞共同培养,可形成软骨样组织,该方法将有可能成为软骨缺损及关节盘破损修复的有途径。     

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.     

Quantitative MRI of articular cartilage and its clinical applications

Cartilage is one of the most essential tissues for healthy joint function and is compromised in degenerative and traumatic joint diseases. There have been tremendous advances during the past decade using quantitative MRI techniques as a noninvasive tool for evaluating cartilage, with a focus on assessing cartilage degeneration during osteoarthritis (OA). In this review, after a brief overview of cartilage composition and degeneration, we discuss techniques that grade and quantify morphologic changes as well as the techniques that quantify changes in the extracellular matrix. The basic principles, in vivo applications, advantages, and challenges for each technique are discussed. Recent studies using the OA Initiative (OAI) data are also summarized. Quantitative MRI provides noninvasive measures of cartilage degeneration at the earliest stages of joint degeneration, which is essential for efforts toward prevention and early intervention in OA. J. Magn. Reson. Imaging 2013;38:991–1008. © 2013 Wiley Periodicals, Inc.     

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.     

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.     

微骨折术治疗膝关节软骨损伤修复效果T2 star mapping评价研究

目的 本研究应用MRI对关节镜下微骨折法治疗膝关节软骨损伤修复效果进行大体组织形态学评估及定量分析.方法 本研究纳入14例有膝关节软骨损伤症状并接受关节镜下微骨折法治疗的病例进行回顾性病例分析.所有病例的关节软骨损伤均为ICRS分级Ⅲ或Ⅳ,术中测量病变面积为2～8cm^2.1年随访期内所有病例都接受常规MRI序列及T2 star mapping序列扫描（1.5T）.对损伤修复区域采用软骨组织修复磁共振观察评分系统（MOCART）进行评价.采用T2 star mapping序列扫描图像感兴趣区划分的方法对修复区域及自身正常软骨所测量的T2＊弛豫值进行分析比较.结果 1年随访期软骨修复区MOCART评分为59.50±23.90,相邻本体软骨组织评分为65.21±21.84,与软骨修复组间比较无显著差异.软骨修复区和邻近正常自体软骨组织T2＊弛豫时间分别为（31.14±9.26）ms和（32.93±11.69）ms,修复区软骨组织质地与正常软骨组织相近.结论 经关节镜下微骨折法修复膝关节软骨损伤后1年随访观察期内,MRI软骨扫描可见软骨损伤区填充良好.经T2＊测量值分析证实软骨修复组织可以达到与邻近正常透明软骨相近的组织结构.     

不同细胞移植修复兔全层关节软骨缺损的比较研究

目的 :比较软骨细胞、骨髓基质细胞及成纤维细胞对全层关节软骨缺损的修复作用。材料和方法 :取幼兔的软骨细胞、骨髓基质细胞及成纤维细胞 ,共 3种有生成软骨潜力的细胞进行体外分离培养 ;以聚乳酸 (PLA)为载体 ,将培养的原代细胞植入PLA支架上 ,形成细胞 -PLA复合物。于 2 8只成年新西兰大白兔的股骨滑车关节面上造成直径 4 5mm、深 3 0mm的全层关节软骨缺损 ,将 3种细胞 -PLA复合物分别植入关节软骨缺损处。植入细胞 -PLA复合物为实验组 ,单纯植入PLA支架为对照组。术后 6周、12周观察缺损修复情况及新生组织类型。结果 :软骨细胞移植组为软骨样组织修复 ,分界明显 ,甲苯胺兰及Ⅱ型胶原染色阳性 ;软骨下骨部分重建 ;细胞排列紊乱。骨髓基质细胞移植组为软骨样组织修复 ,分界不明显 ,甲苯胺兰及Ⅱ型胶原染色阳性 ;软骨下骨重建良好 ,软骨下潮线恢复 ;细胞排列趋于正常。成纤维细胞移植组为纤维组织修复 ,甲苯胺兰及Ⅱ型胶原染色阴性 ;软骨下潮线消失。对照组为纤维组织修复。结论 :软骨细胞、骨髓基质细胞移植修复软骨缺损明显优于成纤维细胞及对照组。骨髓基质细胞与软骨细胞移植组的修复结果无统计学差异 ,但骨髓基质细胞修复组织的细胞排列有序 ,软骨下骨重建良好 ,与周围组织融合密切 ,更接近正?     

Basic science of articular cartilage and osteoarthritis

Articular cartilage is a specialized tissue uniquely suited for load distribution with a low-friction articulating surface. Its compressive and tensile properties are determined by its matrix and fluid composition, and are maintained by chondrocytes in the homeostatic joint. Osteoarthritis (OA) is increasingly understood as a family of disorders in which the biomechanical properties of cartilage are altered and ultimately fail as the tissue is degraded by local proteases. Mechanically mediated and cytokine-mediated pathways of cartilage degeneration have been identified in the pathogenesis of OA. Further insight into the basic science of cartilage and OA is necessary to develop diagnostic and treatment strategies for this pervasive disease.     

Effect of in vitro culture on a chondrocyte-fibrin glue hydrogel for cartilage repair

Research in tissue engineering has been focused on articular cartilage repair for more than a decade. Some pioneristic studies involved the use of hydrogels such as alginate and fibrin glue which still possess valuable potential for cartilage regeneration. One of the main issues in cartilage tissue engineering is represented by the ideal maturation of the construct, before in vivo implantation, in order to optimize matrix quality and integration. The present study was focused on the effect of in vitro culture on a fibrin glue hydrogel embedding swine chondrocytes. We performed an evaluation of the immunohistochemical and biochemical composition and of the biomechanical properties of the construct after 1 and 5 weeks of culture. We noticed that chondrocytes survived in the fibrin glue gel and enhanced their synthetic activity. In fact, DNA content remained stable, while all indices of cartilage matrix production increased (GAGs content, immunohistochemistry for collagen II and safranin-o staining). On the other hand, the biomechanical properties remained steady, indicating a gradual substitution of the hydrogel scaffold by cartilaginous matrix. This demonstrates that an optimal preculture could provide the surgeon with a better engineered cartilage for implantation. However, whether this more mature tissue will result in a more efficient regeneration of the articular surface still has to be evaluated in future investigations.     

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.     

组织工程在创伤修复中的应用

创伤修复涉及到自体、同种异体组织移植及人工材料替代。上世纪80年代中期出现的组织工程学,为创伤修复提供了新的方向,即用活的细胞接种在可降解支架材料上,经体外培养后植入体内,修复组织缺损,重建功能。本文根据最新文献,介绍了组织工程的主要基础研究成果及临床应用的经验。     

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.     

超声对兔关节软骨损伤的修复作用

目的 探讨低强度脉冲超声对兔膝关节软骨损伤的修复作用。方法 于33只新西兰兔股骨髁问窝软骨面处钻孔，伤后左后肢膝关节缺损处以低强度脉冲超声辐照，右后肢予以假照作为对照。分别于伤后2，4和8周处死，做大体及病理组织学观察。结果 超声辐照组修复组织成熟度较对照组高，修复时间明显提前，第8周辐照组修复组织已接近正常透明软骨组织；对照组修复组织较为幼稚，接近纤维软骨组织。结论 低强度脉冲超声能促进兔关节软骨损伤的修复