Autologes Resurfacing der Gelenkoberfläche

The treatment of deep cartilage defects is still a problem for which there is no satisfactory solution. Full-thickness defects of the articular cartilage rarely heal spontaneously. Techniques currently available for the treatment of chondral defects include abrasion, drilling, micro-fracturing, tissue autografts, allografts, and cell transplantation. Osteochondral autograft transplantation is currently the only surgical cartilage repair technique known to lead to the formation and retention of genuine hyaline articular cartilage. The Draenert method using a diamond bone-cutting system is an effective procedure for resurfacing the joint affected by localised cartilaginous defects, even when there is also severe bone loss. The problem of donor-side morbidity can be minimalised by filling the defect caused by harvesting with a press-fit cylinder of cancellous bone protected with periosteum.     

Autologous osteochondral transplantation

The surface of diarthrodial joints is covered by hyaline cartilage whose regeneration capacity is extremely limited. Conventional surgical techniques enable repair of full-thickness articular cartilage defects only by fibrous cartilage having poor mechanical properties. Recently, new techniques have been developed to provide hyaline or hyaline-like repair tissue in the treatment of full-thickness cartilage defects. Autologous osteochondral transplantation involves press-fit implantation of both bone and cartilage obtained from healthy articular surface. The principal indication for this technique is unifocal full-thickness chondral or osteochondral defects measuring 1 to 4 square centimeters. This surgical procedure can be performed openly or arthroscopically. The graft should be placed vertically and evenly to the joint surface. Although short-term and mid-term results are satisfactory, several problems have been reported including donor site morbidity, damage to cartilage, and incongruity and incorporation of the graft. Autologous osteochondral transplantation provides viable osteochondral units at a single stage and eliminates the need for culturing chondrocytes which is quite expensive. Currently, no surgical technique or medical treatment provide complete healing of articular cartilage defects. Autologous osteochondral transplantation is an important stage worthy of improvement in this respect.     

Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee.

This study utilizes a canine model to quantify changes in articular cartilage 15-18 weeks after a knee joint is subjected to surgical treatment of isolated chondral defects. Clinical and experimental treatment of articular cartilage defects may include implantation of matrix materials or cells, or both. Three cartilage repair methods were evaluated: microfracture, microfracture and implantation of a type-II collagen matrix, and implantation of an autologous chondrocyte-seeded collagen matrix. The properties of articular cartilage in other knee joints subjected to harvest of articular cartilage from the trochlear ridge (to obtain cells for the cell-seeded procedure) were also evaluated. Physical properties (thickness, equilibrium compressive modulus, dynamic compressive stiffness, and streaming potential) and biochemical composition (hydration, glycosaminoglycan content, and DNA content) of the cartilage from sites distant to the surgical treatment were compared with values measured for site-matched controls in untreated knee joints. No significant differences were seen in joints subjected to any of the three cartilage repair procedures. However, a number of changes were induced by the harvest operation. The largest changes (displaying up to 3-fold increases) were seen in dynamic stiffness and streaming potential of patellar groove cartilage from joints subjected to the harvest procedure. Whether the changes reported will lead to osteoarthritic degeneration is unknown, but this study provides evidence that the harvest procedure associated with autologous cell transplantation for treatment of chondral defects may result in changes in the articular cartilage in the joint.     

Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees

OBJECTIVE: There is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints. DESIGN: Twenty-four knees of 24 patients with knee osteoarthritis (OA) who underwent a high tibial osteotomy comprised the study group. Adherent cells in bone marrow aspirates were culture expanded, embedded in collagen gel, transplanted into the articular cartilage defect in the medial femoral condyle and covered with autologous periosteum at the time of 12 high tibial osteotomies. The other 12 subjects served as cell-free controls. RESULTS: In the cell-transplanted group, as early as 6.3 weeks after transplantation the defects were covered with white to pink soft tissue, in which metachromasia was partially observed. Forty-two weeks after transplantation, the defects were covered with white soft tissue, in which metachromasia was observed in almost all areas of the sampled tissue and hyaline cartilage-like tissue was partially observed. Although the clinical improvement was not significantly different, the arthroscopic and histological grading score was better in the cell-transplanted group than in the cell-free control group. CONCLUSIONS: This procedure highlights the availability of autologous culture expanded bone marrow mesenchymal cell transplantation for the repair of articular cartilage defects in humans.     

Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilage of both knees in other rabbits. The cultured allogenic chondrocytes were transplanted into the defect in the right knees and closed with a periosteal flap, while the defects in the left knees served as controls and were closed with a periosteal flap alone, without chondrocytes. Healing of the defects was assessed at 12 weeks by histological studies. Allogenic chondrocyte transplantation significantly increased the amount of newly formed repair tissue (P=0.04) compared with that found in the control knees. The histological quality score of the repair tissue was significantly better (P=0.05), with more hyaline characteristics in the knees treated with allogenic chondrocytes than in the control knees. Articular cartilage defects treated with allogenic chondrocyte transplantation result in better repair tissue formation with hyaline characteristics than those in control knees.     

异体骨基质海绵吸附自体骨髓细胞修复关节软骨的实验研究

在兔股骨髌股关节面上造成软骨缺损,采用同种异体骨基质海绵吸附自体骨髓细胞移植,分期取材.通过肉眼、光镜、电镜观察软骨修复过程中的组织学形态.结果显示骨髓细胞在关节腔内血供差、低氧压及滑液的环境中具有较好的成软骨作用.认为自体骨髓细胞来源充足、易采取,创伤小,无不良并发症,无排斥反应.有可能成为一种修复关节软骨缺损的新途径.     

Advances in articular cartilage repair

Many joint and systemic disorders may lead to cartilage defects. Partial thickness defects of the articular cartilage do not have healing potential. When the lesion reaches the subchondral bone, spontaneous healing may be observed, but consists of fibrocartilaginous tissue. The main efforts for cartilage repair are targeted at filling of the cartilage defect with a tissue that possesses the same mechanical properties with hyaline cartilage and the consolidation of this tissue with the native articular cartilage. There are various arthroscopic techniques and although they provide pain relief, they do not restore the damaged cartilage. Osteochondral transplantation is more effective in dealing with small or medium size full thickness defects, but further efforts are required in order to reduce the donor site morbidity, marginal necrosis and partial covering of the defect.     

新鲜同种异体骨软骨移植修复软骨缺损

目的联合应用新鲜同种异体骨软骨移植,和局部注射碱性成纤维细胞生长因子(basic fibroblast growthfactor,bFGF),探讨能否促进关节软骨缺损区新生软骨的形成,提高软骨缺损修复的成功率。方法48只青紫兰兔,96个实验关节,随机分为A、B、C、D组。无菌条件下制作骨软骨缺损模型。在A组缺损区单纯植入新鲜的同种异体骨软骨,B组单纯局部注射重组人bFGF,C组局部注射bFGF后同时植入新鲜的同种异体骨软骨,D组用作空白对照。术后第4、8、12周作大体观察、X线摄片、组织学检查及免疫组化检查。结果移植加注射bFGF组促进软骨缺损修复的效果均好于其他组,图像分析仪进行软骨细胞记数有显著差异(P<0.05),有统计学意义。修复软骨型胶原免疫组化染色强阳性。结论采用新鲜的同种异体骨软骨移植及联合应用碱性成纤维细胞生长因子,二者能起交互作用,促进了新生软骨的形成。     

Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports

This study assessed the effectiveness of autologous bone marrow stromal cell transplantation for the repair of full-thickness articular cartilage defects in the patellae of a 26-year-old female and a 44-year-old male. These two patients presented in our clinic because their knee pain prevented them from walking normally. After thorough examination, we concluded that the knee pain was due to the injured articular cartilage and decided to repair the defect with bone marrow stromal cell transplantation. Three weeks before transplantation, bone marrow was aspirated from the iliac crest of each patient. After erythrocytes had been removed by use of dextran, the remaining nucleated cells were placed in culture. When the attached cells reached subconfluence, they were passaged to expand in culture. Adherent cells were subsequently collected, embedded in a collagen gel, transplanted into the articular cartilage defect in the patellae, and covered with autologous periosteum. Six months after transplantation, clinical symptoms (pain and walking ability) had improved significantly and the improvement has remained in effect (5 years and 9 months posttransplantation in one case, and 4 years in the other), and both patients have been satisfied with the outcome. As early as 2 months after transplantation, the defects were covered with tissue that showed slight metachromatic staining. Two years after the first and 1 year after the second transplantation, arthroscopy was performed and the defects were repaired with fibrocartilage. Results indicate autologous bone marrow stromal cell transplantation is an effective approach in promoting the repair of articular cartilage defects.     

Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC)

Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis.     

The osteochondral dilemma: review of current management and future trends

The management of articular cartilage defects remains challenging and controversial. Hyaline cartilage has limited capacity for self‐repair and post‐injury cartilage is predominantly replaced by fibrocartilage through healing from the subchondral bone. Fibrocartilage lacks the key properties that characterize hyaline cartilage such as capacity for compression, hydrodynamic permeability and smoothness of the articular surface. Many reports relate compromised function associated with repaired cartilage and loss of function of the articular surface. Novel methods have been proposed with the key aim to regenerate hyaline cartilage for repair of osteochondral defects. Over the past decade, with many exciting developments in tissue engineering and regenerative cell‐based technologies, we are now able to consider new combinatorial approaches to overcome the problems associated with osteochondral injuries and damage. In this review, the currently accepted surgical approaches are reviewed and considered; debridement, marrow stimulation, whole tissue transplantation and cellular repair. More recent products, which employ tissue engineering approaches to enhance the traditional methods of repair, are discussed. Future trends must not only focus on recreating the composition of articular cartilage, but more importantly recapitulate the nano‐structure of articular cartilage to improve the functional strength and integration of repair tissue.     

异体软骨细胞移植修复猪膝关节软骨缺损的免疫学观察

目的应用同种异体软骨细胞移植修复猪膝关节软骨缺损,评估术后免疫学表现及其修复效果。方法供体为1月龄上海白猪2头,取其膝关节全层软骨片,0.25%胰蛋白酶和0.2%型胶原酶消化,分离培养软骨细胞。受体为2月龄巴马猪8头,在两侧股骨髁关节负重面造成0.5cm×0.5cm软骨缺损,深及软骨下骨。于受体猪双侧膝关节软骨缺损处注入软骨细胞悬液0.2ml,含软骨细胞(1.0～2.0)×106个,密封入口。术前、术后3、5、7、12周分离受体外周血淋巴细胞,检测其与异体软骨细胞混合后的刺激指数(stimulationindex,SI);术后5、7、24周取修复区软骨及软骨下骨观察局部组织学反应。结果术后3、5、7、12周受体外周血淋巴细胞SI分别为1.457±0.062、1.739±0.142、1.548±0.047和1.216±0.028,较术前(1.102±0.034)增高,且差异均有统计学意义(P<0.05);SI术后3周开始升高,5周达高峰,7、12周后开始逐渐下降;3、7、12周SI与5周比较差异均有统计学意义(P<0.05)。组织学观察:术后5周,出现较多的炎性浸润,分散于软骨下骨、修复组织与正常软骨的整合部等;7周,炎性浸润开始减退,仅在软骨下骨可见;24周,缺损处修复软骨与周围软骨整合良好。结论异体软骨细胞移植后,免疫反应一般在移植早期开始出现,并逐渐达到高峰,但随着软骨基质的重新合成,免疫反应也逐渐下降,并最终修复全层关节软骨缺损。     

Articular cartilage repair using tissue engineering technique--novel approach with minimally invasive procedure

Articular cartilage has very limited potential to spontaneously heal, because it lacks vessels and is isolated from systemic regulation. Although there have been many attempts to treat articular cartilage defects, such as drilling, microfracture techniques, soft tissue grafts or osteochondral grafts, no treatment has managed to repair the defects with long-lasting hyaline cartilage. Recently, a regenerative medicine using a tissue engineering technique for cartilage repair has been given much attention in the orthopedic field. In 1994, Brittberg et al. introduced a new cell technology in which chondrocytes expanded in monolayer culture were transplanted into the cartilage defect of the knee. As a second generation of chondrocyte transplantation, since 1996 we have been performing transplantation of tissue-engineered cartilage made ex vivo for the treatment of osteochondral defects of the joints. This signifies a concept shift from cell transplantation to tissue transplantation made ex vivo using tissue engineering techniques. We have reported good clinical results with this surgical treatment. However, extensive basic research is vital to achieve better clinical results with this tissue engineering technique. This article describes our recent research using a minimally invasive tissue engineering technique to promote cartilage regeneration.     

Articular cartilage. Anatomy, injury, and repair

Articular cartilage plays a vital role in joint morphology. An understanding of articular cartilage anatomy and physiology will enable the physician to more fully appreciate its function and necessity. Articular cartilage is made up of four basic biological layers or zones. Each zone possesses attributes necessary to make articular cartilage as a whole strong, durable, and more able to withstand shear and axial forces through a joint. Cartilage metabolism is relatively slow in comparison with other tissues; hence, it is much more difficult for defects in cartilage to heal spontaneously. There are many ways in which articular cartilage can incur damage. Mechanical injury, be it acute or insidious, causes cartilage to fissure and fracture. This results in painful and inflamed joints along with disruption of the cartilage. Metabolic diseases also can produce joint destruction, inflammation, and pain. The resultant defects fail to heal spontaneously because of slow metabolism of cartilage. These chondral defects eventually may penetrate subchondral bone. Disruption of the layers of cartilage eventually will cause collapse and loss of integrity of the entire joint apparatus as a whole. More than 250 years ago, Hunter stated, "Ulcerated cartilage is a troublesome thing--once [it is] destroyed it is not repaired." Articular cartilage defects are very difficult to repair effectively. Cartilage defects can heal spontaneously, if the defect extends to subchondral bone. The reparative substance, fibrocartilage, is less durable and much less smooth. There are many techniques and procedures in which chondral or osteochondral defects can be filled. Promoting subchondral bleeding is the method most commonly used clinically. This allows pleuripotent cells to fill the defect with eventual fibrocartilage. Implants are gaining favor as a method of inducing a more pure, hyaline-like cartilage into cartilage defects. Gene therapy and tissue engineering are at the forefront of cartilage research today. Cartilage injury and repair remains today a very difficult topic of study. Understanding the anatomy of articular cartilage, the pathomechanics of injury, and methods available for cartilage repair, will help the physician more adequately approach treatment options.     

Histopathology of failed osteoarticular shell allografts

Fresh cadaveric osteochondral fragment allografts were used to replace damaged articular surfaces of knee joints. Of the original 100 patients, 22 experienced graft failure necessitating graft removal. From these patients, a total of 44 osteochondral allografts were extirpated between 12 and 84 months after insertion. These were examined radiologically, histologically, and ultrastructurally. The bone and bone marrow were necrotic and had undergone variable replacement by host bone, which appeared to be independent of the duration of the graft. The articular cartilage showed degenerative changes ranging from fibrillation to erosion. Viable donor cartilage was present as late as seven years, proving that fresh graft cartilage can survive transplantation. Host bone interfaced with the cartilage, but in 14 grafts there was focal invasion of the cartilage. In some grafts, pannus formation with resorption of cartilage was evident. There was no histologic evidence of transplant rejection. This study is encouraging because hyaline cartilage has been shown to survive for as long as seven years and because bone can be replaced in a homogeneous fashion if the correct biomechanical conditions are met.     

自体骨软骨移植与含富集骨髓干细胞松质骨移植修复兔关节软骨缺损

目的:评价自体骨软骨移植与含富集骨髓干细胞松质骨镶嵌移植两种方法修复全层关节软骨缺损的生物学特征和效果。方法:采用新西兰大白兔制作左右后肢全层软骨缺损模型,分别进行自体骨软骨镶嵌移植、含富集骨髓干细胞松质骨镶嵌移植修复,对照组不作任何修复,每组12只。术后第4、8、12周处死动物取材,分别进行膝关节活动度测定、大体观察、光镜观察与电镜观察。结果:移植实验组在第12周时均能以类透明软骨组织修复缺损,对照组为纤维肉芽组织。形态学检查表明,两种方法均能以类透明软骨组织覆盖缺损,骨软骨移植组无明显免疫排斥现象,随着时间延长,修复高度逐渐增加。骨软骨移植组同含富集骨髓干细胞松质骨镶嵌移植组效果无显著差别。结论:骨软骨移植、含富集骨髓干细胞松质骨镶嵌移植两种方法均能以类透明软骨组织修复全层关节软骨缺损,含富集骨髓干细胞松质骨镶嵌移植更适用于较大面积软骨缺损的修复。     

Repair of articular cartilage defects with cultured chondrocytes on polysulphonic membrane: experimental studies in rabbits

INTRODUCTION: Autologous osteochondral transplantation is one method that can be used to create hyaline or hyaline-like repair in a defect area. The purpose of the present study was to repair full-thickness articular cartilage defects in 9 rabbit knee joints with autologous cultured chondrocytes. METHODS: An articular cartilage defect was created on the patellar groove of the femur. The defect was filled with chondrocytes cultured in vitro and placed into the knee on a polysulphonic membrane. At 8 weeks after the operation, the reparative tissue was analyzed macroscopically and histologically. RESULTS: At 8 weeks after the operation, the surfaces of the reparative tissue were smooth, and the defects were filled with mature hyaline cartilage in 5 cases. In 2 cases, the reparative hyaline cartilage was immature and there was worse integration of grafted tissue into the adjacent normal cartilage. In 2 cases, the surface of the grafted area was irregular, and the reparative tissue was disintegrated and incompletely differentiated. CONCLUSION: The results suggest that transplantation of autologous chondrocytes cultured in vitro and placed into the knee on polysulphonic membrane is effective in repairing an articular cartilage defect.     

Recent advances toward the clinical application of bone morphogenetic proteins in bone and cartilage repair

Inefficient healing of bony and cartilaginous defects is a common situation encountered by orthopedic surgeons. Enhancing the regenerative potential of bone and articular cartilage has the potential for profound applications in treatment of nonunions, large segmental bone and cartilage defects, and arthritis. The bone morphogenetic proteins (BMPs) encode a highly conserved class of signaling factors that possess the ability to induce ectopic cartilage and bone formation in vivo. Bone morphogenetic protein family members are expressed during limb development, endochondral ossification, and early fracture and cartilage repair. Loss-of-function and gain-of-function studies have demonstrated the necessity and sufficiency of these genes, respectively, in regulating both cartilage and bone development. Several recent animal studies have demonstrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. A limited number of clinical trials using BMPs in human beings have been reported, and these agents are currently available for clinical use within and outside the United States. Current challenges to be met are the development of efficient delivery systems to present BMP proteins or genes to target sites and to enhance their duration and function at these locations.     

Gene therapy for cartilage repair

AIM: Articular cartilage has very limited intrinsic healing capacity. Although numerous attempts to repair full-thickness articular cartilage defects have been conducted, no methods have successfully regenerated long-lasting hyaline cartilage. One of the most promising procedures for cartilage repair is tissue engineering accompanied by gene therapy. METHOD: With gene therapy, genes encoding for therapeutic growth factors can be expressed at a high level in the injured site for an extended period of time. Chondrocytes have been intensively studied for cell transplantation in articular cartilage defects. RESULTS: However, recent studies have shown that chondrocytes are not the only candidate for cartilage repair. Muscle-derived cells have been found capable of delivering genes and represent a good vehicle to deliver therapeutic genes to improve cartilage repair. More importantly, recent studies have suggested the presence of pluripotent stem cells in muscle-derived cells. CONCLUSION: New techniques of cell therapy and molecular medicine for the treatment of cartilage lesions are currently undergoing clinical trials. This paper will summarize the current status of gene therapy for cartilage repair and its future application.     

Surgical technique for articular cartilage transplantation to full-thickness cartilage defects in the knee joint

Focal arthritic defects in the knee lead to pain, swelling, and dysfunction. Treatment of the defects has includeddrilling, abrasion, and grafting. This report describes our surgical technique of autogenous articular cartilage grafting of arthritic and traumatic articular cartilage lesions. Articular cartilage grafting can be performed as a single arthroscopic outpatient procedure. The mixture of articular cartilage and cancellous bone appears to provide a supportive matrix for cartilage formation. Pain relief is excellent if careful surgical technique and a defined rehabilitation program is followed. Further collagen typing data and additional biopsies will reveal more about the durability of the newly formed cartilage.