Value of autologous transplantation of osteo-chondral paste in reconstruction of experimental cartilage defects. Part II. Microscopic analysis of integration with surrounding cartilage, structural integrity and subchondral bone reconstruction in repair tissue]

INTRODUCTION: A limited ability of the cartilage to heal after trauma was the reason to start research on new methods concerning better cartilage reconstruction. The aim of the study was evaluation of repair tissue integration with surrounding cartilage, its structural integrity and subchondral bone reconstruction after osteo-chondral paste transplantation. MATERIAL AND METHODS: Full thickness defect (IV degree--ICRS scale) on distal rabbit femur joint surface was made. Three groups were specified: A--defect with paste graft (cartilage and contiguous bone collected from joint surface, crushed into homogenous paste; B--defect with the paste graft covered with periosteum; C--defect left unfilled. The follow-up periods were established at 4, 8, 12 weeks. Repair tissue was evaluated microscopically according to modified O'Driscoll scale. RESULTS: Newly formed tissue was well integrated with surrounding cartilage in group A (paste graft). That trade of repair tissue in group A was much better than in other groups, especially in late observations. Structural integrity of tissue filling the defect was similar to integrity of normal cartilage in groups A and C, but tissue formed in group C didn't represent a hyaline-like cartilage character. In all the examined groups reconstruction of subchondral bone exhibited similar rate. 12 weeks from the procedure, around 80% of subchondral bone was rebuilt. The obtained results indicate, that osteo-chondral paste autologous transplantation in cartilage defects treatment effects with forming well integrated (structurally and with surrounding cartilage) cartilage tissue, of almost complete subchondral bone rebuilding.     

Value of autologous chondrocyte transplantation in experimental cartilage defects reconstruction. Part III--Microscopic analysis of reconstructed cartilage thickness and integration with surrounding tissue]

Lack of cartilage vascularization is the reason of its low regenerative potential. The aim of this part of the study was microscopic evaluation of repair tissue thickness and its integration with surrounding cartilage, after autologous chondrocyte transplantation. MATERIAL AND METHODS: Repair of partial thickness cartilage defect (ICRS III(o) grade) on distal femur joint surface was evaluated (25 adolescent rabbits). Procedures were performed in two groups: I--autologous chondrocyte transplantation under periosteal flap, II--periosteal graft. Chondrocytes were isolated from the cartilage specimens by enzymatic digestion and cultured in vitro. The follow-up periods were established at 4, 8, 12 weeks. Repair tissue was evaluated microscopically according to modified O'Driscoll scale. RESULTS: In group I, 8 weeks after the procedure most of defects were filled with the newly formed tissue almost completely. Regenerate thickness after 4 and 12 weeks usually exceeded 1/2 of surrounding cartilage. In group II, 8 weeks after the procedure regenerate thickness amounted to at least 1/2 of surrounding cartilage, but 4- and 12-week observation revealed the decreased repair tissue thickness. In group I, 4 weeks after the procedure regenerative tissue was well integrated with surrounding cartilage, and this trait still gradually increased with time. In group II, there was partial integration or no integration of repair tissue with surrounding cartilage. CONCLUSION: Obtained results indicate, that tissue formed after autologous chondrocyte transplantation with use of periosteal flap was better in its thickness and integration with surrounding cartilage, as compared to tissue formed after use of periosteum alone. Autologous chondrocyte transplantation can not guarantee complete filling of the cartilage defect with the graft tissue and full integration with surrounding cartilage, without three-dimensional scaffold application.     

Value of osteo-chondral paste autologous transplantation in experimental cartilage defects reconstruction. Part III--Microscopic analysis of reconstructed cartilage thickness and surface regularity]

INTRODUCTION: A limited ability of the cartilage to heal after trauma was the reason to start research on new methods concerning better cartilage reconstruction. The aim of the study was evaluation of repair tissue thickness and surface regularity after osteochondral paste transplantation. MATERIAL AND METHODS: Full thickness defect (IV(o)--ICRS scale) on distal rabbit femur joint surface was made. Three groups were specified: A--defect with paste graft (cartilage and contiguous bone collected from joint surface, crushed into homogenous paste; B--defect with the paste graft covered with periosteum; C--defect left unfilled. The follow-up periods were established at 4, 8, 12 weeks. Repair tissue was evaluated microscopically according to modified O'Driscoll scale. RESULTS: Newly formed tissue was well integrated with surrounding cartilage in group A (paste graft). That trait of repair tissue in group A was much better than in other groups, especially in late observations. Structural integrity of tissue filling the defect was similar to integrity of normal cartilage in groups A and C, but tissue formed in group C didn't represent a hyaline-like cartilage character. In all the examined groups reconstruction of subchondral bone exhibited similar rate. 12 weeks from the procedure, around 80% of subchondral bone was rebuilt. The obtained results indicate, that osteochondral paste autologous transplantation in cartilage defects treatment effects with forming well integrated (structurally and with surrounding cartilage) cartilage tissue, of almost complete subchondral bone rebuilding.     

Value of autologous chondrocyte transplantation in experimental cartilage defects reconstruction. Part IV--Microscopic analysis of repair tissue degenerative changes (cellularity and signs of necrosis)]

Articular cartilage cells are immersed in semi-solid matrix and isolated from the rest of the body because of lack of nervous fibres, and blood and lymphatic vessels. Trauma and aging processes result in cartilage ultrastructure disorders. Those changes leads to progressive decreasing of durability and rigidity of cartilage. Research on articular cartilage reconstruction focuses on, among other things, reaching by newly formed tissue optimal amount of vital cells. The aim of this part of the study was microscopic evaluation of repair tissue degenerative changes (cellularity and signs of necrosis). MATERIAL AND METHODS: Repair of partial thickness cartilage defect (III tertiary grade) on distal femur joint surface was evaluated (25 adolescent rabbits). Procedures were performed in two groups: I--autologous chondrocyte transplantation under periosteal flap, II--periosteal graft. Chondrocytes were isolated from the cartilage specimens by enzymatic digestion and cultured in vitro. The follow-up periods were established at 4, 8 and 12 weeks. Repair tissue was evaluated microscopically according to modified O'Driscoll scale. RESULTS: Repair tissue cellularity. In group I (with chondrocytes), 4 weeks after the procedure tissue of high cellularity was formed, corresponding in amount of cells to the structure of early differentiated hyaline-like cartilage. Amount of cells slightly decreased with time, as it occurs in maturing cartilage. In group II (without chondrocytes), 4 weeks after the procedure the repair tissue was characterized by small amount of cells, which was decreasing with time. Signs of necrosis. In group I, 4, 8 and 12 weeks after the procedure moderate intensity of necrotic signs was observed. In group II, significant intensity of necrosis signs in all observation periods was observed. CONCLUSION: Obtained results indicate, that autologous chondrocyte transplantation in treatment of partial thickness cartilage defects effects with forming tissue of high cellularity, not degenerating with time, much better as compared to untreated defect.     

Value of autologous chondrocyte transplantation in the reconstruction of experimental cartilage defects. Part I. Extent of defect, macroscopic appearance of reconstructed articular surface and microscopic analysis of predominant tissue]

Articular cartilage defect is one of the main reasons of osteoarthritis. Currently, tissue engineering techniques are the methods concerning better cartilage reconstruction. The aim of this part of the study was macroscopic evaluation of degree of defect feeling, macroscopic appearance of repair tissue and microscopic analysis of predominant tissue after autologous chondrocytes transplantation. Repair of partial thickness cartilage defect on distal part of femur was evaluated (25 adolescent rabbits). Procedures were performed in II groups: I--autologous chondrocytes transplantation under periosteal flap, II--periosteal graft. Chondrocytes were isolated from the cartilage specimens by enzymatic digestion and cultured in vitro. The regenerates were inspected 4, 8 and 12 weeks after the operation. Macroscopic analysis in group I, in most cases revealed filling of the defect with tissue resembling surrounding cartilage. In group II the defect was partially filled, and there was many fissures and cracks in all regenerates. In microscopic analysis in group I, after 4 and 8 weeks following the transplantation the tissue similar to juvenile hyaline cartilage predominated. After 12 weeks it resembled mature hyaline cartilage. In group II, in all cases fibrous cartilage was observed after 4, 8, 12 weeks. Obtained results indicate, that macroscopic and microscopic characteristics of repair tissue after autologous chondrocytes transplantation more closely resembled hyaline cartilage, than in periosteal graft group. 12 weeks after autologous chondrocytes transplantation the repair tissue reached maturity, and demonstrated microscopic characteristics of hyaline-like cartilage. The method of autologous chondrocytes transplantation provides potential for clinical application.     

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.     

Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation

OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.     

Repair of human articular cartilage after implantation of autologous chondrocytes

Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage.     

细胞载体作为软骨修复中的下一代细胞疗法

背景自从第一位患者接受培养自体软骨细胞移植 （ACI） 以来已过去20多年,新型的软骨修复细胞疗法已经出现.自体培养软骨细胞是第一代细胞疗法,它使用的是混悬培养的自体软骨细胞结合骨膜修补.胶原膜覆盖ACI （CACI）是第二代细胞疗法,它使用的是接种了混悬培养软骨细胞的Ⅰ/Ⅲ型胶原膜上.现今,因关节镜移植术的需求而开发出了第三代细胞疗法,也即采用细胞载体或接种了细胞的支架来移植培养的自体软骨细胞.目的 本文综述了目前基质诱导的自体软骨细胞移植 （MACI） 的情况,它是迄今为止使用最广泛的载体系统.本文还探讨了Ⅰ/Ⅲ型胶原膜的特点、与胶原膜相关的细胞行为、手术技术、康复、临床结果和组织修复效果.研究设计 系统回顾.方法通过搜索 Medline 数据库从1949 年成立以来到 2007年12月的数据,找出相关文献;确认出关于细胞行为、制作过程、手术技术和康复方案的基础和临床研究同行评审的文献.具有原始数据以及使用Ⅰ/Ⅲ型胶原膜的基础和临床研究也被纳入.结果 这些研究获得的数据证实使用MACI治疗的患者在临床结果方面有总体改善.观察到视觉模拟疼痛量表（VAS）评分降低（范围在 1.7～5.32 分）,而改良Cincinnati（范围在3.8～34.2分）评分、Lysholm-Gillquist（范围在23.09～47.6分）评分、Tegner-Lysholm（范围在1.39～3.9分）评分和国际膝关节文献委员会分类量表评分（P〈0.05）均有改善.通过关节镜（包括国际软骨修复学会评分）、MRI 和组织学评估,患者也显示出质量良好的（透明样）组织修复,并且术后并发症发生率较低.结论本综述的结果提示：第三代细胞疗法MACI 程序在治疗有症状的、全层关节软骨缺损修复方面是一种大有前景的方法.     

Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective,comparative trial

BACKGROUND: Current methods used to restore the joint surface in patients with localized articular cartilage defects include transplantation of an autologous osteochondral cylinder and implantation of autologous chondrocytes. The purpose of this study was to evaluate the clinical and histological outcomes of these two techniques. METHODS: We performed a prospective clinical study to investigate the two-year outcomes in forty patients with an articular cartilage lesion of the femoral condyle who had been randomly treated with either transplantation of an autologous osteochondral cylinder or implantation of autologous chondrocytes. Biopsy specimens from representative patients of both groups were evaluated with histological staining, immunohistochemistry, and scanning electron microscopy. RESULTS: According to the postoperative Lysholm score, the recovery after autologous chondrocyte implantation was slower than that after osteochondral transplantation at six months (p < or = 0.015), twelve months (p < or = 0.001), and twenty-four months (p < or = 0.012). On the basis of the Meyers score and the Tegner activity score, the results were equally good with the two methods two years after treatment. Histomorphological evaluation of biopsy specimens within two years after autologous chondrocyte implantation demonstrated a complete, mechanically stable resurfacing of the defect in all patients. The tissue consisted mainly of fibrocartilage, while localized areas of hyaline-like regenerative cartilage could be detected close to the subchondral bone. Although a gap remained at the site of the transplantation in all five biopsy specimens examined as long as two years after osteochondral cylinder transplantation, histomorphological analysis and scanning electron microscopy revealed no differences between the osteochondral transplants and the surrounding original cartilage. CONCLUSIONS: Both treatments resulted in a decrease in symptoms. However, the improvement provided by the autologous chondrocyte implantation lagged behind that provided by the osteochondral cylinder transplantation. Histologically, the defects treated with autologous chondrocyte implantation were primarily filled with fibrocartilage, whereas the osteochondral cylinder transplants retained their hyaline character, although there was a persistent interface between the transplant and the surrounding original cartilage. Limitations of our study included the small number of patients, the relatively short (two-year) follow-up, and the absence of a control group.     

Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair.

Traumatic articular cartilage injuries heal poorly and may predispose patients to the early onset of osteoarthritis. One current treatment relies on surgical delivery of autologous chondrocytes that are prepared, prior to implantation, through ex vivo cell expansion of cartilage biopsy cells. The requirement for cell expansion, however, is both complex and expensive and has proven to be a major hurdle in achieving a widespread adoption of the treatment. This study presents evidence that autologous chondrocyte implantation can be delivered without requiring ex vivo cell expansion. The proposed improvement relies on mechanical fragmentation of cartilage tissue sufficient to mobilize embedded chondrocytes via increased tissue surface area. Our outgrowth study, which was used to demonstrate chondrocyte migration and growth, indicated that fragmented cartilage tissue is a rich source for chondrocyte redistribution. The chondrocytes outgrown into 3-D scaffolds also formed cartilage-like tissue when implanted in SCID mice. Direct treatment of full-thickness chondral defects in goats using cartilage fragments on a resorbable scaffold produced hyaline-like repair tissue at 6 months. Thus, delivery of chondrocytes in the form of cartilage tissue fragments in conjunction with appropriate polymeric scaffolds provides a novel intraoperative approach for cell-based cartilage repair.     

Repair of porcine articular cartilage defect with autologous chondrocyte transplantation.

Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype.     

Repair of articular cartilage defects: part II. Treatment options

Articular cartilage injuries result in numerous clinical symptoms, such as pain and decreased functional levels. Current therapeutic options being used include articular surface debridement, such as chondral shaving, abrasion chondroplasty, and subchondral perforation; soft-tissue arthroplasties, such as perichondrial and periosteal grafts; and osteochondral transplantation. None of these therapies, however, has resulted in the successful regeneration of a hyaline-like tissue that withstands normal joint loading and activity over prolonged periods. As a result, research is also being conducted on alternative therapeutic procedures to enhance the repair process and to stimulate the regeneration of a repair tissue with hyaline-like structural and biologic properties. Part I of this paper, which was published in January, discussed the basic science of cartilage healing. Part II presents the treatment options.     

Subchondral Bone Reaction Associated with Chondral Defect and Attempted Cartilage Repair in Goats

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.     

Subchondral Bone Reaction Associated with Chondral Defect and Attempted Cartilage Repair in Goats

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.     

Magnetic resonance imaging of cartilage repair techniques

Magnetic resonance (MR) imaging offers a noninvasive method to assess cartilage repair, allowing objective evaluation of the repair tissue and insight into the natural history of cartilage repair procedures. MR imaging allows assessment of the percent fill, signal morphology of the repair tissue, subchondral bone and three-dimensional geometry of the joint. The information gained from MR imaging therefore plays a valuable role in patient follow-up after cartilage repair. This article discusses the MR imaging techniques available for the assessment of articular cartilage, including quantitative imaging techniques that allow assessment of cartilage biochemistry. The MR imaging appearance and assessment of microfracture, autologous chondrocyte implantation, and osteochondral autograft and allograft transplantation is reviewed.     

Evaluation of articular cartilage with 3D-SPGR MRI after autologous chondrocyte implantation

To assess the maturation process of the cartilage after autologous chondrocyte implantation (ACI), we performed a longitudinal study with three-dimensional spoiled gradient-recalled (3D-SPGR) magnetic resonance imaging (MRI). Five knees of five patients on which ACI of the femoral condyle was performed were studied. The signal intensity of reparative tissue approached that of normal articular cartilage with time. The volume of reparative tissue remained at an almost constant level after implantation. During second-look arthroscopy, the areas on which ACI was performed were covered with hyaline-like cartilage, and the reparative tissue removed by biopsy consisted of normal chondrocytes and extracellular matrix. The increased signal intensity of the reparative tissue represents maturation of implanted autologous chondrocytes. 3D-SPGR MRI is thought to be useful for evaluating reparative tissue after autologous chondrocyte implantation.     

Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7.

BACKGROUND: Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. METHODS: Chondrocytes treated with adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells. RESULTS: Four weeks after surgery AdBMP-7-treated repairs showed an increased level of BMP-7 expression and accelerated healing, with markedly more hyaline-like morphology than control. Quantitative real-time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP-7-treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups. CONCLUSIONS: Implantation of genetically modified chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair tissue in experimental cartilage defects. CLINICAL RELEVANCE: Rehabilitation after cell-based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing.     

Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells

OBJECTIVES: Human bone-marrow stromal cells are believed to be multipotent even in adults. This study assessed the effectiveness of autologous bone-marrow stromal cells, which were embedded within a collagen scaffold, to repair a full-thickness articular cartilage defect in the medial femoral condyle of an athlete. PATIENT AND METHODS: A 31-year-old male judo player suffering from pain in the right knee was reviewed. A 20 x 30-mm full-thickness cartilage defect (International Cartilage Repair Society classification (ICRS) grade IV) was revealed in the weight-bearing area of the medial femoral condyle. With the informed consent of the patient, the defect was treated with autologous bone-marrow stromal cells. Bone marrow was aspirated from the iliac crest of the patient 4 weeks before surgery. After removing the erythrocytes, the remaining cells were expanded in culture. Adherent cells were collected and embedded within a collagen gel, which was transferred to the articular cartilage defect in the medial femoral condyle. The implant was covered with an autologous periosteal flap. RESULTS: Seven months after surgery, arthroscopy revealed the defect to be covered with smooth tissues. Histologically, the defect was filled with a hyaline-like type of cartilage tissue which stained positively with Safranin-O. One year after surgery, the clinical symptoms had improved significantly. The patient had reattained his previous activity level and experienced neither pain nor other complications. CONCLUSIONS: Our findings indicate that the transplantation of autologous bone-marrow stromal cells can promote the repair of large focal articular cartilage defects in young, active patients.     

膝关节软骨损伤的外科治疗进展

关节软骨损伤后,软骨缺损通常缺乏自行修复能力,要求外科修复。传统外科治疗软骨损伤包括关节镜下冲洗清理术、微骨折术、自体骨软骨移植术、异体骨软骨移植术和自体软骨细胞移植等方法。关节冲洗清理术去除了关节内致痛因素,操作简单,应用广泛,早期疗效确切。微骨折术及自体骨软骨移植对小面积的软骨缺损修复较为理想,然而远期临床观察发现钻孔渗透修复的纤维软骨会降低微骨折术后疗效,相对于重建负重区关节面完整性自体骨软骨移植更具有优势。自体软骨细胞移植及异体骨软骨移植适用于更大面积的软骨缺损,异体骨软骨移植术后存活率受到局部排斥反应影响,从而降低了远期疗效。软骨组织工程技术可最大限度地提高自体软骨细胞移植的修复质量,实现修复组织接近透明软骨,但对于累及软骨下骨板、反应性骨水肿、严重骨量丢失或下肢轴线不良具有局限性。近年来许多新技术陆续应用于软骨损伤治疗领域,创伤小、操作简便、恢复快、疗效好、花费低、多技术联合应用的外科修复技术将会成为未来的治疗软骨损伤的重要手段。目前如何提高软骨修复质量,更具抗压、耐磨性,仍亟待解决。