Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

PURPOSE: The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). METHODS: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. RESULTS: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). CONCLUSION: This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. LEVEL OF EVIDENCE: Level I.

Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology.

METHODS: Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice. CONCLUSION: In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk. / Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk.

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cm2 maximum, while autologous chondrocyte implantation is the method of choice for larger cartilage defects. Additionally, matrix-augmented bone marrow stimulation (mBMS) has been included in the recommendation for defects ranging from 1 to 4.5 cm2. For the treatment of smaller osteochondral defects, in addition to osteochondral transplantation (OCT), mBMS is also recommended. For larger defects, matrix-augmented autologous chondrocyte implantation (mACI/mACT) in combination with augmentation of the subchondral bone is recommended.

Long-Term Clinical and MRI Results of Matrix-Assisted Autologous Chondrocyte Implantation for Articular Cartilage Defects of the Knee.

OBJECTIVE: To evaluate the long-term clinical and radiological outcome of matrix-assisted autologous chondrocyte implantation (mACI) for articular cartilage defects in the knee joint. DESIGN: Clinical evaluation was assessed in 21 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) grade IV. Clinical scoring was performed preoperatively and 12 years after transplantation using the International Knee Documentation Committee (IKDC) score, the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes sports activity rating scale. Morphologic evaluation of the repair tissue was assessed by magnetic resonance imaging (MRI) in 14 patients using the Kreuz-Henderson score. RESULTS: Clinical evaluation revealed significant improvement in the IKDC, the Lysholm, the KOOS, and the Noyes score. Morphological evaluation by MRI showed moderate to complete defect filling in 10 of 14 patients, demonstrating normal to nearly normal values in mean 74.29% of all assessed parameters. Significant correlation of the parameter cartilage signal and clinical outcome was found with the IKDC, Lysholm, and KOOS subscales ADL (activities of daily living) and QoL (quality of life). CONCLUSIONS: The clinical and radiological outcomes 12 years after transplantation suggest the confirmation of the promising results of the mid-term follow-up. This study therefore provides first indications that the implantation of mACI might be a suitable option for long-term cartilage repair. Future controlled studies need to address the exact parameters influencing the long-term outcome of mACI.

[Biologic Reconstruction of Full Sized Cartilage Defects of the Hip: A Guideline from the DGOU Group "Clinical Tissue Regeneration" and the Hip Committee of the AGA]. / Biologische Rekonstruktion lokalisiert vollschichtiger Knorpelschäden des Hüftgelenks: Empfehlungen der Arbeitsgemeinschaft "Klinische Geweberegeneration" der DGOU und des Hüftkomitees der AGA.

Background Symptomatic pre-arthritic deformities such as femoroacetabular impingement (FAI) or hip dysplasia often lead to localised cartilage defects and subsequently to osteoarthritis. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) and the hip committee of the AGA (German speaking Society for Arthroscopy and Joint Surgery) provides an overview of current knowledge of the diagnosis and surgical treatment of cartilage defects, in order to infer appropriate therapy recommendations for the hip. Methods Review of FAI and resultant cartilage damage in the hip as reported in published study findings in the literature and discussion of the advantages and disadvantages of different surgical procedures to preserve the joint. Results Most published studies on the surgical treatment of cartilage damage in the hip report defects caused by cam-type FAI at the acetabulum. Development of these defects can be prevented by timely elimination of the relevant deformities. At present, current full-thickness cartilage defects are mostly treated with bone marrow-stimulating techniques such as microfracture (MFx), with or without a biomaterial, and matrix-assisted autologous chondrocyte transplantation (MACT). Osteochondral autologous transplantation (OAT) is not the treatment of choice for isolated full-thickness chondral defects at the hip, because of the unfavourable risk-benefit profile. Due to the relatively short history of cartilage repair surgery on the hip, the studies available on these procedures have low levels of evidence. However, it is already becoming obvious that the experience gained with the same procedures on the knee can be applied to the hip as well. For example, limited healing and regeneration of chondral defects after MFx can also be observed at the hip joint. Conclusions The cartilage surface of the acetabulum, where FAI-related chondral lesions appear, is considerably smaller than the weight-bearing cartilage surface of the knee joint. However, as in the knee joint, MACT is the therapy of choice for full-thickness cartilage defects of more than 1.5 - 2 cm2. Minimally invasive types of MACT (e.g. injectable chondrocyte implants) should be preferred in the hip joint. In cases where a single-stage procedure is indicated or there are other compelling reasons for not performing a MACT, a bone marrow-stimulating technique in combination with a biomaterial covering is preferable to standard MFx. For treatment of lesions smaller than 1.5 - 2 cm2 the indication for a single-stage procedure is wider. As with defects in the knee, it is not possible to determine a definite upper age limit for joint-preserving surgery or MACT in the hip, as the chronological age of patients does not necessarily correlate with their biological age or the condition of their joints. Advanced osteoarthritis of the hip is a contraindication for any kind of hip-preserving surgery. Long-term observations and prospective randomised studies like those carried out for other joints are necessary.

Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus.

Microfracture for the treatment of cartilage defects in the knee joint - A golden standard?

The evidence for the effectiveness of the microfracture procedure is largely derived from case series and few randomized trials. Clinical outcomes improve with microfracture for the most part, but in some studies these effects are not sustained. The quality of cartilage repair following microfracture is variable and inconsistent due to unknown reasons. Younger patients have better clinical outcomes and quality of cartilage repair than older patients. When lesion location was shown to affect microfracture outcome, patients with lesions of the femoral condyle have the best clinical improvements and quality of cartilage repair compared with patients who had lesions in other areas. Patients with smaller lesions have better clinical improvement than patients with larger lesions. The necessity of long postoperative CPM and restricted weight bearing is widely accepted but not completely supported by solid data. Maybe new developments like the scaffold augmented microfracture(6) will show even more consistent clinical and biological results as well as faster rehabilitation for the treatment of small to medium sized cartilage defects in younger individuals. All in all there is limited evidence that micro fracture should be accepted as gold standard for the treatment of cartilage lesions in the knee joint. There is no study available which compares empty controls or non-surgical treatment/physiotherapy with microfracture. According to the literature there is even evidence for self regeneration of cartilage lesions. The natural history of damaged cartilage seems to be written e.g. by inflammatory processes, genetic predisposition and other factors. Possibly that explains the large variety of the clinical outcome after micro fracture and possibly the standard tools for evaluation of new technologies (randomized controlled trials, case series, etc.) are not sufficient (anymore). Future technologies will be evaluated by big data from international registries for earlier detection of safety issues, for detection of subtle but crucial co-factors for failure and osteoarthritis as well as for lower financial burdens affecting industry and healthcare systems likewise.

Cartilage-Repair Innovation at a Standstill: Methodologic and Regulatory Pathways to Breaking Free.

Articular cartilage defects strongly predispose patients to developing early joint degeneration and osteoarthritis, but for more than 15 years, no new cartilage-repair technologies that we know of have been approved by the U.S. Food and Drug Administration. Many studies examining novel approaches to cartilage repair, including cell, tissue, or matrix-based techniques, have shown great promise, but completing randomized controlled trials (RCTs) to establish safety and efficacy has been challenging, providing a major barrier to bringing these innovations into clinical use. In this article, we review reasons that surgical innovations are not well-suited for testing through RCTs. We also discuss how analytical methods for reducing bias, such as propensity scoring, make prospective observational studies a potentially viable alternative for testing the safety and efficacy of cartilage-repair and other novel therapies, offering the real possibility of therapeutic innovation.

Significantly worse isokinetic hamstring-quadriceps ratio in patellofemoral compared to condylar defects 4 years after autologous chondrocyte implantation.

PURPOSE: Detailed biomechanical analysis including isokinetic muscle strength measurements after autologous chondrocyte implantation (ACI) are still rare, but might be of crucial importance for long-term outcomes. The present prospective study was performed to evaluate whether defect location had any influence on clinical and biomechanical outcomes 4 years after ACI. METHODS: Forty-four patients with full-thickness cartilage defects ICRS grade III B and C underwent ACI and were assigned to two groups, the femoral condyle group or the patellofemoral joint group. Clinical scores were gathered preoperatively and 6, 12 and 48 months after implantation using the International Knee Documentation Committee (IKDC) score and the International Cartilage Repair Society (ICRS) form. Isokinetic strength measurements were performed 48 months postoperatively comparing healthy and operated knee joint of each patient. RESULTS: Clinical scores (ICRS, IKDC) showed continuous significant (p < 0.05) improvement over the study period for both groups. Isokinetic muscle strength measurements showed significantly reduced maximum strength capacities for the operated knee joint compared to the healthy knee in both groups (p < 0.05). Hamstring-quadriceps ratios of the operated extremity revealed a significant change in physiological muscle balancing (ratios >1.0) based on significantly impaired extensor muscle strength in the patellofemoral joint group. CONCLUSION: All patients showed significant strength deficits on the operated extremity 4 years after ACI. Furthermore, the patellofemoral compartment in particular showed significantly worse hamstring-quadriceps ratios compared to condylar defects. Consequently, more efforts should be made to restore muscular strength especially of the quadriceps and the rehabilitation protocol should be adjusted accordingly. LEVEL OF EVIDENCE: II.

Correlation between 3D microstructural and 2D histomorphometric properties of subchondral bone with healthy and degenerative cartilage of the knee joint.

Cartilage degeneration of the knee joint is considered to be a largely mechanically driven process. We conducted a microstructural and histomorphometric analysis of subchondral bone samples of intact cartilage and in samples with early and higher- grade arthritic degeneration to compare the different states and correlate the findings with the condition of hyaline cartilage. These findings will enable us to evaluate changes in biomechanical properties of subchondral bone during the evolution of arthritic degeneration, for which bone density alone is an insufficient parameter. From a continuous series of 80 patients undergoing implantation of total knee endoprosthesis 30 osteochondral samples with lesions macroscopically classified as ICRS grade 1b (group A) and 30 samples with ICRS grade 3a or 3b lesions (group B) were taken. The bone samples were assessed by 2D histomorphometry (semiautomatic image analysis system) and 3D microstructural analysis (high-resolution micro-CT system). The cartilage was examined using the semiquantitative real-time PCR gene expression of collagen type I and II and aggrecan. Both histomorphometry and microstructural and biomechanical analysis of subchondral bone in groups A and B consistently revealed progressive changes of both bone and cartilage compared with healthy controls. The severity of cartilage degeneration as assessed by RT PCR was significantly correlated with BV/TV (Bone Volume Fraction), Tb.Th (Trabecular Thickness) showed a slight increase. Tb.N (Trabecular Number), Tb.Sp (Trabecular separation) SMI (Structure Model Index), Conn.D (Connectivity Density) and DA (Degree of Anisotropy) were inversely correlated. We saw sclerotic transformation and phagocytic reticulum cells. Bone volume fraction decreased with an increasing distance from the cartilage with the differences compared with healthy controls becoming greater in more advanced cartilage damage. The density of subchondral bone alone is considered an unreliable parameter for classifying changes evolving over time. The progressive damage of subchondral bone seen in the present study correlates well with cartilage changes. Trabecular orientation is also impaired, which explains the changes in biomechanical parameters and the inadequate load transfer and excessive loading of cartilage. Besides subchondral bone density, which in turn correlates with cartilage thickness, other parameters such as structure model index and grade of anisotropy best reflect mechanical properties such as Young modulus, compressive strength, tensile stress, and failure energy. However, it remains unclear whether the mechanical interaction of the mineralized subchondral tissues with articular cartilage works vice versa. The possibility of a biochemical signalling from the degenerating cartilage via the synovial fluid and bone- cartilage crosstalks via subchondral pores may indeed explain a certain depth-dependency of subchondral bone changes.

Is gender influencing the biomechanical results after autologous chondrocyte implantation?

PURPOSE: The influence of gender on the biomechanical outcome after autologous chondrocyte implantation (ACI) including isokinetic muscle strength measurements has not been investigated. The present prospective study was performed to evaluate gender-specific differences in the biomechanical function 48 months after ACI. METHODS: Fifty-two patients (mean age 35.6 ± 8.5 years) that met our inclusion criteria, underwent ACI with Bioseed C(®) and were evaluated with the KOOS score preoperatively, 6, 12 and 48 months after surgery. At final follow-up, 44 out of the 52 patients underwent biomechanical evaluation with isokinetic strength measurements of both knees. All data were evaluated separately for men and women and compared for each time interval using the Mann-Whitney U test. RESULTS: Clinical scores improved significantly over the whole study period (p < 0.05). Male patients demonstrated significantly better scores during the follow-up in the KOOS score (p < 0.05). Isokinetic strength measurements after 48 months revealed a significant strength deficit of the treated knee in all test modes compared to the healthy extremity (p < 0.05). Furthermore, male patients achieved significantly higher strength values compared to female patients (p < 0.05). CONCLUSIONS: ACI is a viable treatment option for full-thickness chondral defects in the knee of both genders. Isokinetic muscle strength measures are significantly worse in women (p < 0.05), but physiological and may play a role for the explanation of gender-specific results after ACI.

Long-term outcomes after first-generation autologous chondrocyte implantation for cartilage defects of the knee.

BACKGROUND: Autologous chondrocyte implantation (ACI) represents an established surgical therapy for large cartilage defects of the knee joint. Although various studies report satisfying midterm results, little is known about long-term outcomes. PURPOSE: To evaluate long-term clinical and magnetic resonance imaging (MRI) outcomes after ACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between January 1997 and June 2001, a total of 86 patients were treated with ACI for isolated cartilage defects of the knee. The mean patient age at the time of surgery was 33.3 ± 10.2 years, and the mean defect size was 6.5 ± 4.0 cm(2). Thirty-four defects were located on the medial femoral condyle and 13 on the lateral femoral condyle, while 6 patients were treated for cartilage defects of the trochlear groove and 17 for patellar lesions. At a mean follow-up of 10.9 ± 1.1 years, 70 patients (follow-up rate, 82%) treated for 82 full-thickness cartilage defects of the knee were available for an evaluation of knee function using standard instruments, while 59 of these patients were additionally evaluated by 1.5-T MRI to quantify the magnetic resonance observation of cartilage repair tissue (MOCART) score. Clinical function at follow-up was assessed by means of the Lysholm score, the International Knee Documentation Committee (IKDC) score, and the Knee injury and Osteoarthritis Outcome Score (KOOS). Patient activity was assessed by the Tegner score. In addition, pain on a visual analog scale (VAS) and patient satisfaction were evaluated separately. RESULTS: At follow-up, 77% reported being "satisfied" or "very satisfied." The mean IKDC score at follow-up was 74.0 ± 17.3. The mean Lysholm score improved from 42.0 ± 22.5 before surgery to 71.0 ± 17.4 at follow-up (P < .01). The mean pain score on the VAS decreased from 7.2 ± 1.9 preoperatively to 2.1 ± 2.1 postoperatively. The mean MOCART score was 44.9 ± 23.6. Defect-associated bone marrow edema was found in 78% of the cases. Nevertheless, no correlation between the MOCART score and clinical outcome (IKDC score) could be found (Pearson coefficient, r = 0.173). CONCLUSION: First-generation ACI leads to satisfying clinical results in terms of patient satisfaction, reduction of pain, and improvement in knee function. Nevertheless, full restoration of knee function cannot be achieved. Although MRI reveals lesions in the majority of the cases and the overall MOCART score seems moderate, this could not be correlated with long-term clinical outcomes.

Influence of sex on the outcome of autologous chondrocyte implantation in chondral defects of the knee.

BACKGROUND: Sex-specific outcomes have been reported in anterior cruciate ligament reconstruction as well as in osteoarthrosis progression, but there are currently no related published data on autologous chondrocyte implantation (ACI). The present prospective study was performed to investigate sex-dependent differences in the results after ACI. HYPOTHESIS: The clinical and magnetic resonance imaging (MRI) results after ACI of the knee are influenced by the patient's sex. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The midterm clinical and MRI results of a cell-based fibrin-polymer graft for the treatment of full-thickness cartilage defects were evaluated preoperatively and 6, 12, and 48 months after surgery in 52 patients (male:female ratio, 25:27; average age, 35.6 years). Depending on the sex and the location of the defects (femoral condyles, n = 32; patellofemoral compartment, n = 20), patients were assigned to 4 different groups. Baseline clinical scores were compared with follow-up data by paired Wilcoxon tests for the Lysholm score and the International Knee Documentation Committee (IKDC) scoring system. Sex-specific differences were evaluated with the Mann-Whitney U test. The MRI evaluation was performed with the Henderson score at final follow-up. RESULTS: Clinical scores improved in all groups over the whole study period (P < .05). Compared with female patients, male patients achieved significantly better results in the Lysholm score at all time intervals and in the IKDC score at 6 and 12 months after surgery (P < .05). In a subgroup analysis, female patients with patellar defects had the worst results in both clinical scores. With the available number of patients, MRI evaluation at 48 months after surgery revealed no significant difference in defect fill between male and female patients (P > .05). The Pearson correlation coefficient between both clinical scores and the MRI parameters of defect fill and cartilage signal was significant (P < .05). CONCLUSION: Autologous chondrocyte implantation is a promising treatment option for full-thickness cartilage defects of male and female knee joints. Female patients with patellar defects have worse prognostic factors.

Semiquantitative analysis of ECM molecules in the different cartilage layers in early and advanced osteoarthritis of the knee joint.

The study was conducted to examine the expression of collagen type I and II in the different cartilage layers in relation to other ECM molecules during the progression of early osteoarthritic degeneration in human articular cartilage (AC). Quantitative real-time (RT)-PCR and colorimetrical techniques were used for calibration of Photoshop-based image analysis in detecting such lesions. Immunohistochemistry and histology were performed with 40 cartilage tissue samples showing mild (ICRS grade 1b) respectively moderate/advanced (ICRS grade 3a or 3b) (20 each) osteoarthritis compared with 15 healthy biopsies. Furthermore, we quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorimetrically. The digitized images of histology and immunohistochemistry stains were analyzed with Photoshop software. T-test and Spearman correlation analysis were used for statistical analysis. In the earliest stages of AC deterioration the loss of collagen type II was associated with the appearance of collagen type I, shown by increasing amounts of collagen type I mRNA. During subsequent stages, a progressive loss of structural integrity was associated with increasing deposition of collagen type I as part of a natural healing response. A decrease of collagen type II is visible especially in the upper fibrillated area of the advanced osteoarthritic samples, which then leads to an overall decrease. Analysis of proteoglycan showed losses of the overall content and a loss of the classical zonal formation. Correlation analysis of the proteoglycan Photoshop measurements with the RT-PCR revealed strong correlation for Safranin O and collagen type I, medium for collagen type II, alcian blue and glycoprotein but weak correlation with PCR aggrecan results. Photoshop based image analysis might become a valuable supplement for well known histopathological grading systems of lesioned articular cartilage. The evidence of collagen type I production early in the OA disease process coupled with the ability of chondrocytes to up-regulate collagen type II production suggests that therapeutic agents that suppress collagen type I production and increase collagen type II production may enable chondrocytes to generate a more effective repair response.

Autologous chondrocyte implantation (ACI) for the treatment of large and complex cartilage lesions of the knee.

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. 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.

Repair of focal cartilage defects with scaffold-assisted autologous chondrocyte grafts: clinical and biomechanical results 48 months after transplantation.

BACKGROUND: Scaffold-assisted autologous chondrocyte implantation is a clinically effective procedure for cartilage repair, but biomechanical evaluations are still missing. PURPOSE: This study was conducted to assess the clinical efficacy, including biomechanical analyses, of BioSeed-C treatment for traumatic and degenerative cartilage defects of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors evaluated the midterm clinical and biomechanical outcome of BioSeed-C, a cell-based fibrin-polymer graft for the treatment of cartilage defects. Clinical outcome at 4-year follow-up was assessed in 52 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) stage III and IV. Clinical scoring was performed preoperatively and 48 months after implantation using the Lysholm score, the International Knee Documentation Committee (IKDC) score, the ICRS score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes score. Cartilage regeneration was assessed by magnetic resonance imaging (MRI) using the Henderson-Kreuz score. Biomechanical evaluation was performed by isokinetic strength measurements, comparing healthy and operated knee of each patient. RESULTS: Clinical evaluation showed significant improvement in the Lysholm (from 51.8 preoperatively to 80.7 at 48 months postoperatively), IKDC (from 47.5 to 71.5), ICRS (from 3.8 to 2.0), KOOS (subcategory pain from 62 to 78, symptoms from 68 to 76, activities of daily living from 68 to 85, sports from 19 to 55, and quality of life from 30 to 55), and Noyes (from 31 to 59) scores (P ≤ .001) 48 months after implantation of BioSeed-C compared with the preoperative situation. The MRI evaluations showed moderate to complete defect filling in 43 of 44 treated patients. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years. Isokinetic evaluation showed significantly reduced maximum strength capacities for knee flexion and extension at the operated knee compared with the healthy knee (P < .05). CONCLUSION: The clinical outcomes 4 years after graft implantation are good despite a persisting strength deficit. Implanting BioSeed-C is a promising treatment option for cartilage defects of the knee. More emphasis should be put on the rehabilitation of muscular strength.

Comparison of arthroscopic and open assessment of size and grade of cartilage defects of the knee.

PURPOSE: The purpose of our study was to compare arthroscopic versus open measurement of cartilage defects and determination of defect grade according to the International Cartilage Repair Society (ICRS) classification. METHODS: Arthroscopic determination of defect size and grade according to the ICRS classification of 450 focal cartilage defects in 407 patients who underwent autologous chondrocyte implantation was compared with definite findings at the time of open knee surgery. Results were analyzed based on defect location, defect size, and experience of the treating surgeon. RESULTS: Open evaluation of all cartilage defects showed a mean size of 4.54 ± 2.11 cm², whereas arthroscopic determination resulted in a significantly larger mean defect size of 5.69 ± 1.81 cm² (P < .001, r = 0.757). This observation was found in all subgroups concerning defect location and experience of the treating surgeon (P < .001). Overestimation was pronounced among inexperienced surgeons (all P < .01) and in smaller defects (P < .01). Concerning grading of the defect according to the ICRS classification, there was a consensus in 80.9% of the cases when arthroscopic grading was compared with open grading. No differences were found based on defect location or experience of the treating surgeon (P > .05). CONCLUSIONS: Although a high correlation was found between arthroscopic and open evaluation of the cartilage defect size, there is a significant overestimation of the cartilage defect size during arthroscopy. This observation is independent of defect location. Smaller defects and inexperienced surgeons are factors that make an overestimation of defect size more likely. Arthroscopic detection and estimation of the full-thickness cartilage defects according to the ICRS classification seem reliable. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Long-term durability of autologous chondrocyte implantation: a multicenter, observational study in US patients.

BACKGROUND: Autologous chondrocyte implantation for full-thickness lesions of the distal femur has demonstrated good short- to midterm clinical improvement. However, long-term durability (>5 years) of autologous chondrocyte implantation has not been evaluated in US patients to date. HYPOTHESIS: Patients who improve from baseline to early follow-up will sustain improvement at later follow-up. STUDY DESIGN: Case series, Level of evidence, 4. METHODS: Cartilage Repair Registry patients with full-thickness distal femur lesions who were treated with autologous chondrocyte implantation before December 31, 1996 and had modified overall Cincinnati scores at baseline and 1- to 5-year follow-up scores were re-evaluated at 6- to 10-year follow-up. Autologous chondrocyte implantation durability was determined by comparing early (1-5 years) to long-term (6-10 years) outcomes. Adverse events and treatment failures were recorded. Results Seventy-two patients met eligibility criteria (at baseline: mean age, 37 years; mean lesion size, 5.2 cm(2); and overall condition score, 3.4 points [poor]). Eighty-seven percent of patients (47 of 54) who improved at the earlier follow-up period sustained a mean improvement in overall condition score of 3.8 points from baseline to the later follow-up period (P < .001). From baseline to 10-year follow-up (mean follow-up, 9.2 years), 69% improved, 17% failed, and 12.5% reported no change from baseline. Most failures (75% [9 of 12]) occurred at a mean follow-up of 2.5 years. Thirty patients (42%) had 42 operations after autologous chondrocyte implantation; 24 operations (57%) occurred in patients who met the study definition of failure. CONCLUSION: Treatment with autologous chondrocyte implantation for large, symptomatic, full-thickness lesions of the distal femur can result in early improvement that is sustained at longer follow-up (up to 10 years) in the majority of patients.

Changes in content and synthesis of collagen types and proteoglycans in osteoarthritis of the knee joint and comparison of quantitative analysis with Photoshop-based image analysis.

INTRODUCTION: The different cartilage layers vary in synthesis of proteoglycan and of the distinct types of collagen with the predominant collagen Type II with its associated collagens, e.g. types IX and XI, produced by normal chondrocytes. It was demonstrated that proteoglycan decreases in degenerative tissue and a switch from collagen type II to type I occurs. The aim of this study was to evaluate the correlation of real-time (RT)-PCR and Photoshop-based image analysis in detecting such lesions and find new aspects about their distribution. PATIENTS: We performed immunohistochemistry and histology with cartilage tissue samples from 20 patients suffering from osteoarthritis compared with 20 healthy biopsies. Furthermore, we quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorimetrically. Using Adobe Photoshop the digitized images of histology and immunohistochemistry stains of collagen type I and II were stored on an external data storage device. The area occupied by any specific colour range can be specified and compared in a relative manner directly from the histogram using the "magic wand tool" in the select similar menu. In the image grow menu gray levels or luminosity (colour) of all pixels within the selected area, including mean, median and standard deviation, etc. are depicted. Statistical Analysis was performed using the t test. METHOD: With the help of immunohistochemistry, RT-PCR and quantitative RT- PCR we found that not only collagen type II, but also collagen type I is synthesized by the cells of the diseased cartilage tissue, shown by increasing amounts of collagen type I mRNA especially in the later stages of osteoarthritis. RESULTS: A decrease of collagen type II is visible especially in the upper fibrillated area of the advanced osteoarthritic samples, which leads to an overall decrease. Analysis of proteoglycan showed a loss of the overall content and a quite uniform staining in the different zones compared to the healthy cartilage with a classical zonal formation. Correlation analysis of the proteoglycan Photoshop measurements with the RT-PCR using Spearman correlation analysis revealed strong correlation for Safranin O and collagen type I, medium for collagen type II and glycoprotein but weak correlation between PCR aggrecan results. CONCLUSION: Photoshop-based image analysis might become a valuable supplement for well known histopathological grading systems of lesioned articular cartilage.