Related Articles
Introduction
Second-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed®-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee.
Methods
Clinical outcome after 4-year clinical follow-up was assessed in 19 patients with preoperatively radiologically confirmed osteoarthritis and a Kellgren-Lawrence score of 2 or more. Clinical scoring was performed before implantation of the graft and 6, 12, and 48 months after implantation using the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) score, and the International Cartilage Repair Society (ICRS) score. Cartilage regeneration and articular resurfacing were assessed by magnetic resonance imaging (MRI) 4 years after implantation of the autologous cartilage graft.
Results
Significant improvement (P < 0.05) of the Lysholm and ICRS scores was observed as early as 6 months after implantation of BioSeed®-C and remained stable during follow-up. The IKDC score showed significant improvement compared with the preoperative situation at 12 and 48 months (P < 0.05). The KOOS showed significant improvement in the subclasses pain, activities of daily living, and knee-related quality of life 6 months as well as 1 and 4 years after implantation of BioSeed®-C in osteoarthritic defects (P < 0.05). MRI analysis showed moderate to complete defect filling with a normal to incidentally hyperintense signal in 16 out of 19 patients treated with BioSeed®-C. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years.
Conclusions
The results show that the good clinical outcome achieved 1 year after implantation of BioSeed®-C remains stable over the course of a period of 4 years and suggest that implanting BioSeed®-C is a promising treatment option for the repair of focal degenerative defects of the knee.
doi:10.1186/ar2638
PMCID: PMC2688178
PMID: 19265548
Background
Complex cartilage lesions of the knee including large cartilage defects, kissing lesions, and osteoarthritis (OA) represent a common problem in orthopaedic surgery and a challenging task for the orthopaedic surgeon. As there is only limited data, we performed a prospective clinical study to investigate the benefit of autologous chondrocyte implantation (ACI) for this demanding patient population.
Methods
Fifty-one patients displaying at least one of the criteria were included in the present retrospective study: (1.) defect size larger than 10 cm2; (2.) multiple lesions; (3.) kissing lesions, cartilage lesions Outerbridge grade III-IV, and/or (4.) mild/moderate osteoarthritis (OA). For outcome measurements, the International Cartilage Society's International Knee Documentation Committee's (IKDC) questionnaire, as well as the Cincinnati, Tegner, Lysholm and Noyes scores were used. Radiographic evaluation for OA was done using the Kellgren score.
Results and Discussion
Patient's age was 36 years (13-61), defects size 7.25 (3-17.5) cm2, previous surgical procedures 1.94 (0-8), and follow-up 30 (12-63) months. Instruments for outcome measurement indicated significant improvement in activity, working ability, and sports. Mean ICRS grade improved from 3.8 preoperatively to grade 3 postoperatively, Tegner grade 1.4 enhanced to grade 3.39. The Cincinnati score enhanced from 25.65 to 66.33, the Lysholm score from 33.26 to 64.68, the Larson score from 43.59 to 79.31, and Noyes score from 12.5 to 46.67, representing an improvement from Cincinnati grade 3.65 to grade 2.1. Lysholm grade 4 improved to grade 3.33, and Larson grade 3.96 to 2.78 (Table 1), (p < 0.001). Patients with kissing cartilage lesions had similar results as patients with single cartilage lesions.
Mean scores and grades at surgery (Tx) and at follow-up
Conclusion
Our results suggest that ACI provides mid-term results in patients with complex cartilage lesions of the knee. If long term results will confirm our findings, ACI may be a considered as a valuable tool for the treatment of complex cartilage lesions of the knee.
doi:10.1186/1758-2555-3-11
PMCID: PMC3114778
PMID: 21599992
We report our experience of using autologous chondrocyte implantation (ACI) to treat osteochondral defects of the knee in combination with anterior cruciate ligament (ACL) reconstruction. The outcome of symptomatic osteochondral lesions treated with ACI following previous successful ACL reconstruction is also reviewed. Patients were followed for a mean of 23 months. Nine patients underwent ACL reconstruction in combination with ACI. Mean modified Cincinnati knee scores improved from 42 to 69 following surgery. Seven patients described their knee as better and two as the same. A second group of nine patients underwent ACI for symptomatic articular cartilage defects following previous ACL reconstruction. In this group, the mean modified Cincinnati knee score improved from 53 to 62 after surgery. Six patients described their knee as better and three as worse. Combined treatment using ACI with ACL reconstruction is technically feasible and resulted in sustained improvement in pain and function. The results following previous ACL reconstruction also resulted in clinical improvement, although results were not as good as following the combined procedure.
doi:10.1007/s00264-005-0025-3
PMCID: PMC2254665
PMID: 16320051
Background
Autologous chondrocyte implantation (ACI) is considered a promising choice for the treatment of cartilage defects. However, the application of ACI to osteoarthritic patients is, in general, contraindicated. The purpose of this study is to evaluate the efficiency of three-dimensionallystructured ACI (3D-ACI; CaReS) in a rat model of knee osteoarthritis (OA).
Methods
OA-like degenerative changes in the articular cartilage were created by transecting the anterior cruciate ligament (ACLT) in athymic nude rats. Two weeks later, CaReS was transplanted at the cartilage injury sites created by micro-drilling in the patella groove (Chondrocyte-implanted (CI) group: CaReS collagen with human chondrocytes; Collagen group: CaReS collagen without cells; and Sham group: sham operation; n = 15/group).
Results
Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis demonstrated the expression of human-specific type 2 collagen and Sry-type high-mobility-group box 9 (SOX9) in the CI group—not in the other groups—throughout the study period. Double immunohistochemistry for human-specific type 2 collagen and human leukocyte antigen-abacavir (HLA-ABC) at week 4 showed positive staining in the CI group only. Macroscopic assessment showed better repair at the cartilage defect sites in the CI group, compared to the other groups. Histological assessment with toluidine blue staining showed that the thickness of the articular cartilage and semi-quantitative histological scores were higher in the CI group than in the other groups up to week 20.
Conclusions
We demonstrate, for the first time, that 3D-ACI is effective in repairing cartilage defects in a rat model of ACLT-induced OA.
doi:10.3109/03009734.2011.552812
PMCID: PMC3078539
PMID: 21352090
Chondrocyte implantation; geriatrics; knee osteoarthritis; orthopedics
We report the 8-year clinical and radiographic outcome of an adolescent patient with a large osteochondral defect of the lateral femoral condyle, and ipsilateral genu valgum secondary to an epiphyseal injury, managed with autologous chondrocyte implantation (ACI) and supracondylar re-alignment femoral osteotomy. Long-term clinical success was achieved using this method, illustrating the effective use of re-alignment osteotomy in correcting mal-alignment of the knee, protecting the ACI graft site and providing the optimum environment for cartilage repair and regeneration. This is the first report of the combined use of ACI and femoral osteotomy for such a case.
doi:10.1186/1758-2555-3-5
PMCID: PMC3068953
PMID: 21418566
Autologous chondrocyte implantation (ACI) is the most widely used cell-based surgical procedure for the repair of articular cartilage defects. Challenges to successful ACI outcomes include limitation in defect size and geometry as well as inefficient cell retention. Second-generation ACI procedures have thus focused on developing three-dimensional constructs using native and synthetic biomaterials. Clinically significant and satisfactory results from applying autologous chondrocytes seeded in fibrin within a biodegradable polymeric material were recently reported. In the future, third-generation cell-based articular cartilage repair should focus on the use of chondroprogenitor cells and biofunctionalized biomaterials for more extensive and permanent repair.
doi:10.1186/ar2310
PMCID: PMC2212558
PMID: 18021426
Young patients with early osteoarthritis wishing to remain functionally active have limited treatment options. Existing studies examining the use of autologous chondrocyte implantation (ACI) have included patients with early degenerative changes; however, none specifically investigated the outcome of ACI with this challenging problem. We prospectively followed 153 patients (155 knees) for up to 11 years after treatment with ACI for early-stage osteoarthritis. Patient pain and function was assessed using WOMAC, modified Cincinnati, SF-36, Knee Society score, and a satisfaction questionnaire. Mean patient age was 38.3 years. On average, 2.1 defects were treated per knee; the mean defect size was 4.9 cm2 and total area per knee was 10.4 cm2. Eight percent of joints were considered treatment failures that went on to arthroplasty and the remaining patients experienced 50% to 75% improvement in WOMAC subscales. Our data suggest that ACI in patients with early osteoarthritis results in clinically relevant reductions in pain and improvement in function. At 5 years postoperatively, 92% of patients were functioning well and were able to delay the need for joint replacement. Given the limited number of treatment options for this subset of patients, autologous chondrocyte implantation may offer improved quality of life for young osteoarthritic patients.
Level of Evidence: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0998-0
PMCID: PMC2795849
PMID: 19653049
BACKGROUND:
Although a variety of strategies have been employed for managing articular cartilage defects in the knee, overall outcomes have not been satisfactory. An alternative option may be autologous chondrocyte transplantation (ACT). However, as this method is still under investigation, here we assessed the efficacy of ACT for human knee defect cartilage repair.
METHODS:
In a randomized clinical trial study, eleven patients (mean age 31.09 years) were enrolled in the study with full thickness cartilage defects in the knee. Arthroscopically, healthy cartilage was obtained, chondrocytes expanded for 2-3 weeks and ACT performed. Clinical status was evaluated before ACT, 6 and 12 months after ACT using the Brittberg-Peterson functional assessment and modified Cincinnati rating score. Magnetic resonance imaging (MRI) findings were evaluated based on the scoring systems used by Sally Roberts and by Henderson.
RESULTS:
Modified Cincinnati rating indicated significant improvement of clinical score before ACT compared to 6 (p = 0.000) and 12 (p = 0.000) months after ACT (from 2.73 before ACT to 7.27, 8.36 and 9.5 at 6, 12, and 48 months after ACT, respectively). Brittberg-Peterson functional assessment indicated a decline from 79.27 to 25.82 and 19.27 at 6 and 12 months post ACT. Further, statistical test demonstrated significant differences 6, 12 and 48 months post ACT (p = 0.007). Evaluation of MRI revealed a score of 6.5 for Henderson criteria and a score of 2.5 for Robert criteria.
CONCLUSIONS:
Our study demonstrated that ACT of the knee provides an excellent treatment for full thickness cartilage defects with outstanding clinical and radiological outcomes.
PMCID: PMC3263096
PMID: 22279451
Articular Cartilage; Full Thickness Cartilage Defect; Autologus Chondrocyte Transplantation; Knee
Fibrin, a homologous polymer, is the natural scaffold of wound healing and therefore a candidate as a carrier for cell transplantation. We explored a novel matrix-based implant cartilage repair composed of both fibrin and hyaluronan in a defined ratio that takes advantage of the biological and mechanical properties of these two elements. The matrix was seeded with autologous chondrocytes expanded in the presence of a proprietary growth factor variant designed to preserve their chondrogenic potential. We prospectively followed eight patients with symptomatic-chronic cartilage defects treated with this carrier. Patients had arthroscopy to harvest autologous chondrocytes then grown in autologous serum. Chondrocytes were cultured in the presence of the FGF variant and then seeded on the fibrin-hyaluronan matrix. About 4 weeks following biopsy, the patients underwent implantation of the constructs by miniarthrotomy. Three of the eight patients had transient effusion. Clinical performance was measured by Lysholm and IKDC scores, MRI, and the need for secondary surgery. The clinical outcome of a 1-year followup demonstrated increase of clinical scores. The MRI followup showed good filling of the defect with tissue having the imaging appearance of cartilage in all patients. Apart from the transient effusion in three patients we observed no other adverse events during the followup.
Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-008-0322-4
PMCID: PMC2584266
PMID: 18528742
Introduction
Matrix-assisted autologous chondrocyte implantation is a well-known procedure for the treatment of cartilage defects, which aims to establish a regenerative milieu and restore hyaline cartilage. However, much less is known about third-generation autologous chondrocyte implantation application in high-level athletes. We report on the two-year follow-up outcome after matrix-assisted autologous chondrocyte implantation to treat a large cartilage lesion of the lateral femoral condyle in a male Caucasian professional football player.
Case presentation
A 27-year-old male Caucasian professional football player was previously treated for cartilage problems of his left knee with two failed microfracture procedures resulting in a 9 cm2 Outerbridge Grade 4 chondral lesion at his lateral femoral condyle. Preoperative Tegner-Lysholm and Brittberg-Peterson scores were 64 and 58, and by the second year they were 91 and 6. An evaluation with magnetic resonance imaging demonstrated filling of the defect with the signal intensity of the repair tissue resembling healthy cartilage. Second-look arthroscopy revealed robust, smooth cartilage covering his lateral femoral condyle. He returned to his former competitive level without restrictions or complaints one year after the procedure.
Conclusions
This case illustrates that robust cartilage tissue can be obtained with a matrix-assisted autologous chondrocyte implantation procedure even after two failed microfracture procedures in a large (9 cm2) cartilage defect. To the best of our knowledge, this is the first case report on the application of the third-generation cell therapy treatment technique, matrix-assisted autologous chondrocyte implantation, in a professional football player.
doi:10.1186/1752-1947-6-173
PMCID: PMC3404975
PMID: 22742735
Articular cartilage damage in the young adult knee, if left untreated, it may proceed to degenerative osteoarthritis and is a serious cause of disability and loss of function. Surgical cartilage repair of an osteochondral defect can give the patient significant relief from symptoms and preserve the functional life of the joint. Several techniques including bone marrow stimulation, cartilage tissue based therapy, cartilage cell seeded therapies and osteotomies have been described in the literature with varying results. Established techniques rely mainly on the formation of fibro-cartilage, which has been shown to degenerate over time due to shear forces. The implantation of autologous cultured chondrocytes into an osteochondral defect, may replace damaged cartilage with hyaline or hyaline-like cartilage. This clinical review assesses current surgical techniques and makes recommendations on the most appropriate method of cartilage repair when managing symptomatic osteochondral defects of the knee. We also discuss the experience with the technique of autologous chondrocyte implantation at our institution over the past 11 years.
doi:10.4103/0019-5413.65136
PMCID: PMC2911921
PMID: 20697474
Cartilage injuries; cartilage repair; cartilage regeneration; autologous chondrocyte implantation
Autologous chondrocyte implantation is being used increasingly for the treatment of cartilage defects. In spite of this, there has been a paucity of objective, standardised assessment of the outcome and quality of repair tissue formed. We have investigated patients treated with autologous chondrocyte implantation (ACI), some in conjunction with mosaicplasty, and developed objective, semiquantitative scoring schemes to monitor the repair tissue using MRI and histology. Results indicate repair tissue to be on average 2.5 mm thick. It was of varying morphology ranging from predominantly hyaline in 22% of biopsy specimens, mixed in 48%, through to predominantly fibrocartilage, in 30%, apparently improving with increasing time postgraft. Repair tissue was well integrated with the host tissue in all aspects viewed. MRI scans provide a useful assessment of properties of the whole graft area and adjacent tissue and is a noninvasive technique for long-term follow-up. It correlated with histology (P = 0.02) in patients treated with ACI alone.
doi:10.1186/ar613
PMCID: PMC154433
PMID: 12716454
cartilage repair; collagens; glycosaminoglycans histology; MRI
Articular cartilage lesions of the glenohumeral joint are an especially difficult clinical problem to manage, particularly in the younger, more active patient. Left untreated, these lesions may progress in the long-term, leading to further pain and disability. While shoulder arthroplasty remains a viable option in older patients with glenohumeral arthritis, concerns over component longevity and loosening in younger patients make it less attractive in that age group. Arthroscopic joint debridement with loose body removal, often with capsular release, has been successful in select, more sedentary patients. More recent techniques, including autologous chondrocyte implantation (ACI), osteochondral grafting (allograft versus autograft), interpositional arthroplasty, and microfracture surgery, have been evaluated for use in the shoulder. These procedures have experienced success in weight bearing joints, including the knee and ankle. Despite the good clinical results in the shoulder with short-term follow-up reported in some small series, the treatment of chondral injuries in the glenohumeral joint remains a challenging problem.
doi:10.1007/s12178-012-9131-1
PMCID: PMC3535081
PMID: 22628177
Glenohumeral arthritis; Microfracture; Autogenous chondrocyte transfer; Osteochondral graft; Interpositional arthroplasty; Sports non-ACL
Biomaterials play pivotal roles in engineering tissue regeneration and repair. To regenerate irregular shaped defects, injectable cell carriers are desirable. Here, we report the development of self-assembled nanofibrous hollow microspheres from star-shaped biodegradable polymers as an injectable cell carrier for tissue regeneration. The nanofibrous hollow microspheres were shown to efficiently accommodate cells and enhance cartilage regeneration over control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount and higher quality cartilage regeneration over the chondrocytes alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair and integration compared to the chondrocytes alone group that simulates the clinically available autologous chondrocyte implantation (ACI) procedure. These results indicate that the nanofibrous hollow microspheres are an excellent cell carrier for cartilage regeneration and are worthy of further investigation towards the aimed clinical application.
doi:10.1038/nmat2999
PMCID: PMC3080435
PMID: 21499313
Objective
To test the hypothesis that platelet-rich fibrin glue (PR-FG) can be used clinically as a scaffold to deliver autologous culture-expanded bone marrow mesenchymal stem cells (BM-MSCs) for cartilage repair and to report clinical results 1 y after implantation of MSCs PR-FG.
Patients and Methods
Autologous BM-MSCs were culture expanded, placed on PR-FG intraoperatively, and then transplanted into 5 full-thickness cartilage defects of femoral condyles of 5 patients and covered with an autologous periosteal flap. Patients were evaluated clinically at 6 and 12 mo by the Lysholm and Revised Hospital for Special Surgery Knee (RHSSK) scores and radiographically by x-rays and magnetic resonance imaging (MRI) at the same time points. Repair tissue in 2 patients was rated arthroscopically after 12 mo using the International Cartilage Repair Society (ICRS) Arthroscopic Score.
Study Design
Case series; level of evidence 4.
Results
All patients’ symptoms improved over the follow-up period of 12 mo. Average Lysholm and RHSSK scores for all patients showed statistically significant improvement at 6 and 12 mo postoperatively (P < 0.05). There was no statistically significant difference between the 6 and 12 mo postoperative clinical scores (P = 0.18). ICRS arthroscopic scores were 8/12 and 11/12 (nearly normal) for the 2 patients who consented to arthroscopy. MRI of 3 patients at 12 mo postoperatively revealed complete defect fill and complete surface congruity with native cartilage, whereas that of 2 patients showed incomplete congruity.
Conclusion
Autologous BM-MSC transplantation on PR-FG as a cell scaffold may be an effective approach to promote the repair of articular cartilage defects of the knee in human patients.
doi:10.1177/1947603510366027
PMCID: PMC3002255
PMID: 21170288
mesenchymal stem cells; platelet-rich plasma; fibrin glue; cartilage; repair
This prospective six-year longitudinal study reviews the clinical outcome of patients undergoing autologous chondrocyte implantation (ACI) and a porcine type I/III collagen membrane cover for deep chondral defects of the knee. We present 57 patients (31 male, 26 female) with a mean age of 31.6 years (range 15–51 years) that have undergone ACI since July 1998. The mean size of the defect was 3.14 cm2 (range 1.0–7.0 cm2). All patients were assessed annually using seven independent validated clinical rating scores with the data analysed using ANOVA. ACI using a porcine type I/III collagen membrane cover produced statistically significant improvements (p < 0.001), maintained for up to six years, in knee symptoms compared to pre-operative levels. This study provides evidence of the medium-term benefit achieved by transplanting autologous chondrocytes to osteochondral defects.
doi:10.1007/s00264-009-0842-x
PMCID: PMC2989043
PMID: 19669763
Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.
doi:10.1007/s00441-011-1243-1
PMCID: PMC3306561
PMID: 22030892
Articular cartilage; Tissue engineering; Chondrocyte; Signaling molecules; Mechanical stimulation
Background
Despite the many studies on chondral injury repair, no outcomes have been evaluated with the Western Ontario and McMaster (WOMAC) Universities osteoarthritis index, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Oxford Knee Score, all of which are specific for evaluating the presence of osteoarthritis.
Materials and methods
We evaluated the clinical progress of patients following autologous chondrocyte implantation (ACI) performed by our Bone and Tissue Bank using a technique in which cells, instead of being introduced to the articular defect in a liquid form, are implanted into a tridimensional matrix of semisolid collagen (Condrograft®). A total of 22 patients underwent the procedure, 15 of whom were available for a 1-year follow-up that included clinical evaluation by WOMAC score before and after surgery and KOOS and the Oxford Knee Score after surgery.
Results
The results were improved WOMAC score from 56.4 before surgery to 16.2 after surgery (P < 0.002), average KOOS score of 83.6, and average Oxford Knee Score of 18.8.
Conclusions
These results indicate that our tridimensional matrix technique effectively improved patients’ quality of life, at least in the short term, and delayed any subsequent procedure. Long-term assessment is necessary to determine the true value of this technique.
doi:10.1007/s10195-009-0069-z
PMCID: PMC2784059
PMID: 19936886
Tridimensional matrix; WOMAC score; Clinical evaluation; Oxford Knee Score; KOOS
Background
Despite the many studies on chondral injury repair, no outcomes have been evaluated with the Western Ontario and McMaster (WOMAC) Universities osteoarthritis index, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Oxford Knee Score, all of which are specific for evaluating the presence of osteoarthritis.
Materials and methods
We evaluated the clinical progress of patients following autologous chondrocyte implantation (ACI) performed by our Bone and Tissue Bank using a technique in which cells, instead of being introduced to the articular defect in a liquid form, are implanted into a tridimensional matrix of semisolid collagen (Condrograft®). A total of 22 patients underwent the procedure, 15 of whom were available for a 1-year follow-up that included clinical evaluation by WOMAC score before and after surgery and KOOS and the Oxford Knee Score after surgery.
Results
The results were improved WOMAC score from 56.4 before surgery to 16.2 after surgery (P < 0.002), average KOOS score of 83.6, and average Oxford Knee Score of 18.8.
Conclusions
These results indicate that our tridimensional matrix technique effectively improved patients’ quality of life, at least in the short term, and delayed any subsequent procedure. Long-term assessment is necessary to determine the true value of this technique.
doi:10.1007/s10195-009-0069-z
PMCID: PMC2784059
PMID: 19936886
Tridimensional matrix; WOMAC score; Clinical evaluation; Oxford Knee Score; KOOS
Introduction:
The Spanish Ministry of Health commissioned the Galician Agency for Health Technology Assessment to monitor and follow-up Autologous Chondrocyte Implantation (ACI) used to treat chondral lesions of the knee in Spain. The objective of this monitoring was to assess efficacy and safety of the technique.
Design:
One-hundred and eleven consecutive patients with knee chondral lesions were included in a multi-center study between January 2001 and January 2005. ACI was used in these patients as a second-line treatment option (or a first-line treatment option if the cause was Osteocondritis dissecans). The Cincinnati score and the Short Form 36 (SF-36) questionnaire were used to assess the patients’ self-reported satisfaction with the outcomes of ACI. A descriptive analysis was performed and non-parametric tests were used to establish correlations and compare results among subgroups. A multivariate analysis was also performed to measure the effect of different variables on changes in the condition of the knee.
Results:
Eighty men (72%) and 31 women (21%) with an age range from 16 to 49 years, underwent ACI surgery. Among these subjects, the most common previous first-line treatment was debridement (64 individuals, 74.4%). The mean size of the lesion treated with ACI was 3.82 cm2, and the most frequent location of the lesion was the inner femoral condyle (53.6%). The patient satisfaction was high or very high in 36 subjects (66.7%). Overall knee joint assessment improved from 4.32 points to 6.78. All SF-36 questionnaire categories improved, notably those related to physical condition.
Conclusions:
The results of this study indicate that ACI is safe; however, further studies are mandated to assess the efficacy of ACI compared to alternative treatment options.
doi:10.2174/1874325001004010014
PMCID: PMC2817880
PMID: 20148094
Chondrocytes; cartilage; clinical trial; implantation; ACI; transplant.
Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible.
doi:10.1007/s00330-006-0333-z
PMCID: PMC1766022
PMID: 16802126
MRI; Articular cartilage; Cartilage repair; Autologous osteochondral transplantation; Autologous chondrocyte implantation
Background and purpose Autologous osteochondral transplantation (OCT) is an established method of treating articular cartilage defects in the knee. However, the potential for donor site morbidity remains a concern. Both the restoration of the original cartilage defect and the evolution of the donor site defects can be evaluated by bone scintigraphy. Thus, we performed a prospective bone scintigraphic evaluation in patients who were treated with OCT.
Patients and methods In 13 patients with a symptomatic articular cartilage defect, bone scintigraphies were obtained preoperatively, 1 year after osteochondral transplantation, and finally at an average follow-up of 4 (2.5–5.5) years. The evolution of scintigraphic activity was evaluated for both the recipient and the donor site. Parallel, clinical scoring was performed using the Lysholm knee scoring scale, the Cincinnati knee rating system, and the Tegner activity score.
Results The bone scintigraphic uptake was elevated at the involved femoral condyle preoperatively, and gradually decreased to normal levels in 7 of 11 cases. The originally normal uptake at the trochlea increased 1 year after transplantation. Then, a gradual decrease in uptake occurred again at this donor site to remain elevated at the final scintigraphy. A correlation was found between elevated scintigraphic activity and the presence of retropatellar crepitus. The mean Lysholm and Cincinnati scores had increased 1 year after transplantation. The mean Tegner score had increased 3 years after transplantation.
Interpretation Elevated bone scintigraphic activity from an osteochondral lesion in the knee can be restored with OCT. However, increased scintigraphic activity is introduced at the donor site, which becomes reduced with longer follow-up. The use of fairly large osteochondral plugs appears to correlate with retropatellar crepitus and increased scintigraphic activity, and is not therefore recommended.
doi:10.3109/17453671003587101
PMCID: PMC2852158
PMID: 21301491
Currently, autologous chondrocyte transplantation (ACT) is used to treat traumatic cartilage damage or osteochondrosis dissecans, but not degenerative arthritis. Since substantial refinements in the isolation, expansion and transplantation of chondrocytes have been made in recent years, the treatment of early stage osteoarthritic lesions using ACT might now be feasible. In this study, we determined the gene expression patterns of osteoarthritic (OA) chondrocytes ex vivo after primary culture and subculture and compared these with healthy chondrocytes ex vivo and with articular chondrocytes expanded for treatment of patients by ACT. Gene expression profiles were determined using quantitative RT-PCR for type I, II and X collagen, aggrecan, IL-1β and activin-like kinase-1. Furthermore, we tested the capability of osteoarthritic chondrocytes to generate hyaline-like cartilage by implanting chondrocyte-seeded collagen scaffolds into immunodeficient (SCID) mice. OA chondrocytes ex vivo showed highly elevated levels of IL-1β mRNA, but type I and II collagen levels were comparable to those of healthy chondrocytes. After primary culture, IL-1β levels decreased to baseline levels, while the type II and type I collagen mRNA levels matched those found in chondrocytes used for ACT. OA chondrocytes generated type II collagen and proteoglycan-rich cartilage transplants in SCID mice. We conclude that after expansion under suitable conditions, the cartilage of OA patients contains cells that are not significantly different from those from healthy donors prepared for ACT. OA chondrocytes are also capable of producing a cartilage-like tissue in the in vivo SCID mouse model. Thus, such chondrocytes seem to fulfil the prerequisites for use in ACT treatment.
doi:10.1186/ar2218
PMCID: PMC2206334
PMID: 17596264
The objective of this study was to determine the clinical outcome of combined bone grafting and matrix-supported autologous chondrocyte transplantation in patients with osteochondritis dissecans of the knee. Between January 2003 and March 2005, 21 patients (mean age 29.33 years) with symptomatic osteochondritis dissecans (OCD) of the medial or lateral condyle (grade III or IV) of the knee underwent reconstruction of the joint surface by autologous bone grafts and matrix-supported autologous chondrocyte transplantation. Patients were followed up at three, six, 12 and 36 months to determine outcomes by clinical evaluation based on Lysholm score, IKDC and ICRS score. Clinical results showed a significant improvement of Lysholm-score and IKDC score. With respect to clinical assessment, 18 of 21 patients showed good or excellent results 36 months postoperatively. Our study suggests that treatment of OCD with autologous bone grafts and matrix-supported autologous chondrocytes is a possible alternative to osteochondral cylinder transfer or conventional ACT.
doi:10.1007/s00264-009-0841-y
PMCID: PMC2989013
PMID: 19626325
Purpose
The aim of this investigation was to study patient-reported long-term clinical outcome, instrumental stablitity and prevalence of radiological osteoarthritis (OA) a minimum of ten years after isolated anterior cruciate ligament (ACL) reconstruction.
Methods
An average of 13.5 years after ACL reconstruction with bone–patellar tendon–bone (BTB) autograft, 73 patients were evaluated. Inclusion criteria consisted of an isolated ACL rupture and reconstruction with BPTB graft with no associated intra-articular lesions, in particular, cartilage alterations or meniscal lesions. Clinical assessment was performed using the International Knee Documentation Committee (IKDC) and Tegner and Lysholm scores. Instrumental anterior laxity testing was carried out with the KT–1000™ arthrometer. Degree of degenerative changes and prevalence of OA were determined using the Kellgren- Lawrence scale.
Results
Mean follow-up was 13.5 years. Mean age was 43.8 years. About 75% of patients were graded A or B according to the IKDC score. The Lysholm score was 90.2 ± 4.8. Radiological assessment reported degenerative changes of grade II OA in 54.2% of patients. Prevalence of grades III or IV OA was found in 20%. The incidence of OA was significantly correlated with stability and function at long-term follow-up.
Conclusion
Arthroscopic ACL reconstruction using BPTB autograft resulted in a high degree of patient satisfaction and good clinical results on long-term follow-up. A higher degree of OA developed in 20% of patients and was significantly correlated with increased anterior laxity at long-term follow-up.
doi:10.1007/s00264-011-1345-0
PMCID: PMC3251675
PMID: 21898038