Autologous chondrocyte implantation in the knee using fibrin

Autologous chondrocyte implantation (ACI) is widely used to treat symptomatic articular cartilage injury of the knee. Fibrin ACI is a new tissue-engineering technique for the treatment of full-thickness articular cartilage defects, in which autologous chondrocytes are inserted into a three-dimensional scaffold provided by fibrin gel. The objective of this study is to document and compare mean changes in overall clinical scores at both baseline and follow-up. Fibrin ACI was used to treat deep cartilage defects of the femoral condyle in 30 patients. There were 24 men and 6 women with a median age of 35 years (range 15–55) and with a mean defect size of 5.8 cm² (range 2.3–12). Clinical and functional knee evaluations were performed using different scoring systems, MRI was performed 24 months postoperatively, and arthroscopy was performed 12 months postoperatively. All patients achieved clinical and functional status improvements following surgery (P < 0.01). The mean scores of the Henderson classification (MRI evaluation) significantly improved from 14.4 to 7 (P = 0.001), and no graft-associated complications were noted. Arthroscopic assessments performed 12 months postoperatively produced nearly normal (grade II) International Cartilage Repair Society scores in 8 of the 10 study patients. Fibrin ACI offers the advantages of technical simplicity, minimal invasiveness, a short surgery time, and easier access to difficult sites than classical ACI. Based on the findings of this clinical pilot study, we conclude that fibrin ACI offers a reliable means of treating articular cartilage defects of the knee.     

移植基质诱导的自体软骨细胞修复关节软骨缺损临床研究

 目的 探讨基质诱导的自体软骨细胞移植修复关节软骨缺损的方法与疗效.方法 2004年11月～2006年11月,对7例膝关节软骨炎患者行关节镜取软骨、基质诱导自体软骨细胞移植(Matrix-induced Autologous chondrocyte implantation,MACI)膜植入术.对患者行MRI检查确定损伤位置,并进行IKDC2000评分.术后按照特定的康复计划进行循序渐进的功能锻炼.结果 随访时间6个月到24个月.术后半年多数患者各项症状逐渐消失,IKDC2000评分大部分增高.复查MRI和关节镜,显示原来缺损的关节软骨已基本修复,并伴有软骨下骨的修复.结论 与传统自体软骨细胞移植(Autologous chondrocyte implantation,ACI)技术相比,利用MACI技术修复软骨缺损具有术后恢复时间短、操作简便、创伤小、生成更多透明软骨等优点,具有良好的应用前景.     

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。     

Osteochondral allografts in the treatment of articular cartilage injuries of the knee

Osteochondral allografts have demonstrated encouraging clinical and scientific success in the treatment of full-thickness articular cartilage defects in multiple anatomic locations including the knee. The use of fresh grafts has shown the greatest potential for clinical success. There has been growing interest in cryopreservation techniques and the use of cryopreserved grafts owing to the delay in obtaining grafts secondary to regulatory testing, encouraging laboratory data surrounding their use, and the potential for more effective tissue banking. This article reviews the indications, operative technique, and clinical outcomes using osteochondral allografts for full-thickness articular cartilage defects in the knee.     

Treatment of deep cartilage defects of the patella with periosteal transplantation

Twenty-six consecutive patients (19 men and 7 women) with a mean age of 31.5 years (range 19–52 years) who suffered from an isolated full-thickness cartilage defect of the patella (area ranged from 0.75 to 20.0 cm²) and disabling knee pain were treated with autologous periosteal transplantation (without any chondrocytes). The duration of symptoms was 59 months (range 11–144 months). During the first 5 postoperative days all patients were treated with continuous passive motion (CPM). This was followed by active motion, slowly progressive strength training, and slowly progressive weight-bearing. After a mean follow-up of 42 months (range 24–76 months), 17 patients (65%) were graded as excellent (were painfree), 8 patients (31%) as good (had pain with strenous knee-loading activities), and 1 patient as poor (had pain at rest). Twenty-two patients (85%) had returned to their previous occupation. Twelve patients (46%) had resumed sports or recreational activities at their former level. Repeated magnetic resonance imaging (MRI) investigations showed progressive, and finally complete, filling of the articular defects. Biopsies taken in five randomly selected cases showed hyaline-like cartilage. Patients with full-thickness cartilage defects of the patella and disabling knee pain can be treated with autologous periosteal transplantation (without any chondrocytes), followed by CPM, and slowly progressive strength training and weight-bearing. We believe this is a good method to accomplish regeneration of articular cartilage and satisfactory clinical results. Received: 25 March 1998 Accepted: 14 April 1998     

The repair of osteochondral defects using an exogenous fibrin clot. An experimental study in dogs.

To evaluate the ability of an exogenous fibrin clot to hasten or optimize the repair of full-thickness articular cartilage defects, 4-mm diameter, full-thickness articular cartilage defects in 20 adult mongrel dogs were packed with an exogenous fibrin clot that had been prepared from each animal. The defects were created in a loaded and unloaded portion of the femoral trochlea. The healing response was then examined using routine histology at various intervals from 2 weeks to 6 months. Both the experimental (clot-filled) and control (empty) defects healed through a proliferation of fibrous connective tissue that eventually modulated into fibrocartilage. However, in the 2-, 4-, and 8-week animals, the experimental defects (both loaded and unloaded) demonstrated a more organized and advanced healing response than did the control defects. This difference was less pronounced in the 12- and 24-week animals. In all specimens, the clot-filled defects healed more uniformly than controls with less surface depression. In general, the unloaded sites were more uniform in healing than the corresponding loaded sites.     

Early postoperative adherence of matrix-induced autologous chondrocyte implantation for the treatment of full-thickness cartilage defects of the femoral condyle

Matrix-induced autologous chondrocyte implantation (MACI) is a tissue-engineering technique for the treatment of full-thickness articular cartilage defects and requires the use of a three-dimensional collagen type I–III membrane seeded with cultured autologous chondrocytes. The cell-scaffold construct is implanted in the debrided cartilage defect and fixed only with fibrin glue, with no periosteal cover or further surgical fixation. In a clinical pilot study, the MACI technique was used for the treatment of full-thickness, weight-bearing chondral defects of the femoral condyle in 16 patients. All patients were followed prospectively and the early postoperative attachment rate, 34.7 days (range: 22–47) after the scaffold implantation, was determined. With the use of high-resolution magnetic resonance imaging (MRI), the transplant was graded as completely attached, partially attached, or detached. In 14 of 16 patients (87.5%), a completely-attached graft was found, and the cartilage defect site was totally covered by the implanted scaffold and repair tissue. In one patient (6.25%), a partial attachment occurred with partial filling of the chondral defect. A complete detachment of the graft was found in one patient (6.25%), which resulted in an empty defect site with exposure of the subchondral bone. Interobserver variability for the MRI grading of the transplants showed substantial agreement (=0.775) and perfect agreement (_w=0.99). In conclusion, the implantation and fixation of a cell-scaffold construct in a deep cartilage defect of the femoral condyle with fibrin glue and with no further surgical fixation leads to a high attachment rate 34.7 days after the implantation, as determined with high resolution MRI.     

Autologous chondrocyte transplantation

Since its introduction in 1987, autologous chondrocyte transplantation (ACT) for the management of full-thickness chondral defects of the knee has gained considerable attention and has renewed interest in cartilage repair. At this time there are patients with 10 to 13 years of follow-up who have continued to benefit from ACT. ACT is indicated for the management of full-thickness femoral articular Outerbridge grade III and IV lesions. Treatment of other surfaces such as the patella and tibia have also been successful. A thorough knowledge of patient selection and indications, good laboratory practices (GLP), standards of cell culturing, meticulous surgical technique, understanding of the normal time course of healing, the appropriate functional postoperative rehabilitation, and the management of specific ACT-related complications are all essential to good clinical outcomes. The success of this procedure with its excellent clinical outcomes and durability of the articular repair have made it a cost-effective procedure comparable to other technologies.     

Silicone rubber: an alternative for repair of articular cartilage defects

Silicone-rubber implants were used to fill full-thickness articular cartilage in the trochlea area of the knee joint in rabbits, for the purpose of studying the long-term influence of silicone-rubber implant on surrounding articular cartilage. Forty eight weeks after surgery, the silicone rubbers were still fitted tightly into the defects; surrounding cartilage showed mild degeneration, better than the control group. Our results showed silicone-rubber implantation for repairing local articular cartilage defects can effectively delay the pathogenetic progression of osteoarthritis.     

Arthroscopic autologous chondrocyte implantation in osteochondral lesions of the talus: mid-term T2-mapping MRI evaluation

Purpose  

Autologous chondrocyte implantation (ACI) in the ankle has become an established procedure to treat osteochondral lesions. However, a non-invasive method able to provide information on the nature of the repair tissue is needed. Recently, MRI T2 mapping was identified as a method capable of qualitatively characterizing articular cartilage. The aim of this study was to evaluate the mid-term results of a series of patients arthroscopically treated by ACI and investigate the nature of the repair tissue by MRI T2 mapping.     

Magnetic resonance imaging of articular cartilage: ex vivo study on normal cartilage correlated with magnetic resonance microscopy

The aims of this study were (a) to compare the MR appearance of normal articular cartilage in ex vivo MR imaging (MRI) and MR microscopy (MRM) images of disarticulated human femoral heads, (b) to evaluate by MRM the topographic variations in articular cartilage of disarticulated human femoral heads, and subsequently, (c) to compare MRM images with histology. Ten disarticulated femoral heads were examined. Magnetic resonance images were obtained using spin-echo (SE) and gradient-echo (GE) sequences. Microimages were acquired on cartilage–bone cylindrical plugs excised from four regions (superior, inferior, anterior, posterior) of one femoral head, using a modified SE sequence. Both MRI and MRM images were obtained before and after a 90 ° rotation of the specimen, around the axis perpendicular to the examined cartilage surface. Finally, MRM images were correlated with histology. A trilaminar appearance of articular cartilage was observed with MRI and with a greater detail with MRM. A good correlation between MRI and MRM features was demonstrated. Both MRI and MRM showed a loss of the trilaminar cartilage appearance after specimen rotation, with greater evidence on MRM images. Cartilage excised from the four regions of the femoral head showed a different thickness, being thickest in the samples excised from the superior site. The MRM technique confirms the trilaminar MRI appearance of human articular cartilage, showing good correlation with histology. The loss of the trilaminar appearance of articular cartilage induced by specimen rotation suggests that this feature is partially related to the collagen-fiber orientation within the different layers. The MRM technique also shows topographic variations in thickness of human articular cartilage. Received 28 July 1997; Revision received 31 December 1997; Accepted 6 January 1998     

Technical note: the “double eye” technique as a modification of autologous chondrocyte implantation for the treatment of retropatellar cartilage defects

Retropatellar cartilage defects treated with autologous chondrocyte implantation (ACI) are still associated with inferior clinical outcome compared to defects being located on the femoral condyles. This is partly because of the biomechanical characteristics of the patellofemoral section of the joint, in which, in contrast to the medial or lateral compartments of the knee joint, prejudicial shearing forces are dominant. The patellar ridge has a particularly important role in the reduction of these shearing forces. The double eye technique was developed as a modification of ACI with preserving the important patellar ridge for the treatment of retropatellar cartilage defects extending beyond the patellar ridge and involving the medial and lateral retropatellar facets. This technique provides for a separate reconstruction of the medial and the lateral facets by means of ACI, but the ridge region is preserved to maintain the original thickness of cartilage at this point. The present paper describes the “double eye” technique as a modification of autologous chondrocyte transplantation (ACI) for treatment of cartilage defects of the patella, that involve both lateral and medial facets, and gives first clinical results of 11 patients. The average follow-up was 41.6 (±15.0) months, and the average age at diagnosis was 40.4 (±10.1) years. The Lysholm score, the subjective IKDC score, and the ICRS score were the instruments used to measure the outcome. This paper focuses on the introduction of the double eye technique with preservation of the patella ridge in the treatment of retropatellar cartilage lesion. Nevertheless, first clinical results of 11 patients are given, with an average Lysholm score of 75 (±14) points and an average subjective IKDC score of 60 (±14). Objective evaluation according to the criteria of the IKDC score showed very good or good treatment results in 9 of the 11 cases, with only 2 poor results. In conclusion, with the double eye modification presented in this paper, the potential for successful results in the treatment of combined cartilage defects of the medial and lateral facets of the patella is high; it takes into account the specific biomechanical properties of the patella ridge. The procedure needs further evaluation in clinical studies involving larger numbers of patients so that the indications can be determined more precisely.     

Treatment of patellofemoralarticular cartilage injuries with autologous chondrocyte implantation

Autologous chondrocyte implantation (ACI) has successfully been used to repair chondral injuries of the knee. Articular cartilage defects of the patella and trochlea represent a class of cartilage lesions of the knee that have recently been considered an increasing indication for treatment with ACI. These lesions often differ from condyae lesions, having a different etiology and coexisting pathologic conditions in the knee associated with them. Patellar and trochlear cartilage lesions are often associated with patellofemoral maltracking. To obtain good results with these cartilage injuries with ACI, it is essential to address the underlying maltracking issues. Additionally, the contours of the patellar and trochlear cartilage differ from that of the condyles, requiring a modification in the standard technique of periosteal attachment used with condylar lesions. Although results of treating trochlear lesions with ACI have shown good results, the initial reports of treating patellar lesions with ACI were diminished compared to condylar lesions. Recognizing and treating the coexisting pathologic conditions and carefully modifying the standard technique of periosteal attachment has resulted in improved results.     

Magnetic resonance imaging of the femoral trochlea: evaluation of anatomical landmarks and grading articular cartilage in cadaveric knees

Purpose The purpose of the study was to define magnetic resonance imaging (MRI) findings before and after contrast medium opacification of the knee joint in cadaveric specimens to demonstrate anatomical landmarks of the trochlear surface in relation to the neighboring structures, and to evaluate different MRI sequences in the detection of cartilage defects of the trochlear and patellar surface of the knee. Materials and Methods The morphology and relationship of the proximal trochlear surface to the prefemoral fat of the distal femur were investigated by use of different MR sequences before and after intra-articular gadolinium administration into the knee joint in ten cadaveric knees. Anatomic sections were subsequently obtained. In addition, evaluation of the articular surface of the trochlea was performed by two independent observers. The cartilage surfaces were graded using a 2-point system, and results were compared with macroscopic findings. Results Of 40 cartilage surfaces evaluated, histopathologic findings showed 9 normal surfaces, 20 containing partial-thickness defects, and 11 containing full-thickness defects. Compared with macroscopic data, sensitivity of MR sequences for the two reviewers was between 17 and 90%; specificity, 75 and 100%; positive predictive value, 75 and 100%; negative predictive value, 20 and 100%, depending on patellar or trochlea lesions. Interobserver variability for the presence of disease, which was measured using the kappa statistic, was dependent on the MR sequence used between 0.243 and 0.851. Conclusion Magnetic resonance imaging sequences can be used to evaluate the cartilage of the trochlear surface with less accuracy when compared with the results of grading the articular cartilage of the patella.     

MRI-based technique for determining nonuniform deformations throughout the volume of articular cartilage explants.

Articular cartilage is critical to the normal function of diarthrodial joints. Despite the importance of the tissue and the prevalence of cartilage degeneration (e.g., osteoarthritis), the technology required to noninvasively describe nonuniform deformations throughout the volume of the tissue has not been available until recently. The objectives of the work reported in this paper were to 1) describe a noninvasive technique (termed the cartilage deformation by tag registration (CDTR) technique) to determine nonuniform deformations in articular cartilage explants with the use of specialized MRI tagging and image processing methods, 2) evaluate the strain error of the CDTR technique using a custom MRI-compatible phantom material, and 3) demonstrate the applicability of the CDTR technique to articular cartilage by determining 3D strain fields throughout the volume of a bovine articular cartilage explant. A custom MRI pulse sequence was designed to tag and image articular cartilage explants at 7 Tesla in undeformed and deformed states during the application of multiple load cycles. The custom pulse sequence incorporated the "delays alternating with nutations for tailored excitation" (DANTE) pulse sequence to apply tags. This was followed by a "fast spin echo" (FSE) pulse sequence to create images of the tags. The error analysis using the phantom material indicated that deformations can be determined with an error, defined as the strain precision, better than 0.83% strain. When this technique was applied to a single articular cartilage explant loaded in unconfined compression, hetereogeneous deformations throughout the volume of the tissue were evident. This technique potentially can be applied to determine normal cartilage deformations, analyze degenerated cartilage, and evaluate cartilage surgical repair and treatment methodologies. In addition, this technique may be applied to other soft tissues that can be appropriately imaged by MR.     

Autologous chondrocyte implantation: current surgery and rehabilitation

Autologous chondrocyte implantation (ACI) is a treatment option for full-thickness chondral, or osteochondral injuries that are painful, debilitating, and progressive. Goals of surgery and rehabilitation include replacement of damaged cartilage with hyaline or hyaline-like structure, maintained durability to withstand knee intraarticular forces over time with a productive level of function, and restoration of the normal surface congruity of the joint. Intermediate and long-term results are promising in terms of clinical improvement and durability using ACI. This article outlines the surgical technique, the histological and biomechanical principles on which the surgery and rehabilitation process are based, and a recommended rehabilitation protocol.     

Magnetization transfer contrast (MTC) and MTC-subtraction: enhancement of cartilage lesions and intracartilaginous degeneration in vitro

Human articular cartilage from 16 cadaveric or amputated knees was studied using standard magnetic resonance imaging (MRI), on-resonance magnetization transfer contrast (MTC) and MTC-subtraction MRI. Results were compared with subsequent macroscopic and histopathological findings. MTC-subtraction and T2-weighted spin-echo images visualized cartilaginous surface defects with high sensitivity and specificity. MTC and T2-weighted spin-echo images revealed intra-cartilaginous signal loss without surface defects in 80% of the cases, corresponding to an increased collagen concentration. It is concluded that MTC is sensitive to early cartilage degeneration and MTC-subtraction can be helpful in detecting cartilage defects.     

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of human knee articular cartilage: topographical variation and relationships to mechanical properties.

The macromolecular structure and mechanical properties of articular cartilage are interrelated and known to vary topographically in the human knee joint. To investigate the potential of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1, and T2 mapping to elucidate these differences, full-thickness cartilage disks were prepared from six anatomical locations in nonarthritic human knee joints (N = 13). Young's modulus and the dynamic modulus at 1 Hz were determined with the use of unconfined compression tests, followed by quantitative MRI measurements at 9.4 Tesla. Mechanical tests revealed reproducible, statistically significant differences in moduli between the patella and the medial/lateral femoral condyles. Typically, femoral cartilage showed higher Young's (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage (Young's modulus < 0.9 MPa, dynamic modulus < 8 MPa). dGEMRIC moderately reproduced the topographical variation in moduli. Additionally, T1, T2, and dGEMRIC revealed topographical differences that were not registered mechanically. The different MRI and mechanical parameters showed poor to excellent linear correlations, up to r = 0.87, at individual test sites. After all specimens were pooled, dGEMRIC was the best predictor of compressive stiffness (r = 0.57, N = 77). The results suggest that quantitative MRI can indirectly provide information on the mechanical properties of human knee articular cartilage, as well as the site-dependent variations of these properties. Investigators should consider the topographical variation in MRI parameters when conducting quantitative MRI of cartilage in vivo.     

Cartilage defects of the femoral trochlea

Despite improvements in the ability to detect articular cartilage defects of the trochlea, determining the significance of these lesions remains difficult. Physical examination and history taking remain the best way to estimate the clinical impact of these lesions. Debridement and/or microfracture are often initial surgical interventions; these procedures can be expected to provide functional improvement in over 50%, but studies suggest that the amount of improvement deteriorates within 3 years. While initial reports on ACI and osteochondral allografts in the treatment of trochlear defects appear to be more promising solutions, long-term follow-up studies are lacking. Similarly, the effect of tibial tubercle osteotomy combined with cartilage restoration techniques remains unresolved. Nonetheless, based on the limited available evidence, ACI or osteochondral allografts combined with a tibial tubercle osteotomy when appropriate have provided the most durable treatment for these difficult-to-treat lesions.