Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.

[Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)]. / Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks - Empfehlungen der AG Klinische Geweberegeneration der DGOU.

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.

Scientific Evidence Base for Cartilage Injury and Repair in the Athlete.

Soccer players and athletes in high-impact sports are frequently affected by knee injuries. Injuries to the anterior cruciate ligament and menisci are frequently observed in soccer players and may increase the risk of developing an articular cartilage lesion. In high-level athletes, the overall prevalence of knee articular cartilage lesions has been reported to be 36% to 38%. The treatment for athletic patients with articular cartilage lesions is often challenging because of the high demands placed on the repair tissue by impact sports. Cartilage defects in athletes can be treated with microfracture, osteochondral grafting, and autologous chondrocyte implantation. There is increasing scientific evidence for cartilage repair in athletes, with more extensive information available for microfracture and autologous chondrocyte implantation than for osteochondral grafting. The reported rates and times to return to sport at the preinjury level are variable in recreational players, with the best results seen in younger and high-level athletes. Better return to sport is consistently observed for all repair techniques with early cartilage repair. Besides minimizing sensorimotor deficits and addressing accompanying pathologies, the quality of the repair tissue may be a significant factor for the return to sport.

[Use of human progenitor cells in the treatment of cartilage damage]. / Klinische Behandlung von Gelenkknorpelschäden mithilfe autologer Vorläuferzellen.

Articular cartilage defects have virtually no self-healing capacity. As a consequence, a surgical approach for symptomatic grade III/IV defects is required. The application of bone marrow-stimulating techniques (Pridie drilling, microfracture) is only able to reproduce mechanically inferior fibrous cartilage tissue. The minimally invasive surgical technique and low cost with acceptable results in the medium term are the main reasons for the application of these techniques. The combination of microfracture and biomaterials, i.e., the AMIC technique, has not yet proved that the disadvantages of the marrow stimulation techniques can be overcome. At present, only laboratory cultivated autologous chondrocytes are able to restore a biomechanically superior cartilage layer. By selecting the appropriate cell fraction in conjunction with the controlled release of differentiating growth factors, sufficient cartilage regeneration also appears to be achievable on the basis of bone marrow aspirate. This is the subject of experimental studies of bone marrow aspirates and autologous growth factors with encouraging initial results.

[Current treatment for cartilage damage in the patellofemoral joint]. / Aktuelle Behandlung des Knorpelschadens im Patellofemoralgelenk.

Joint cartilage damage in adults has practically no tendency to self healing. Symptomatic grade III/IV damage requires surgical treatment. There are special challenges involved in cartilage damage in the patellofemoral joint as the complicated biomechanics of the joint is often combined with dysplasia. All tissue regeneration measures are based on the recruitment of cells. The synovial cells available in the joint can be differentiated to fibrous cartilage under certain mechanical conditions; however, they cannot sufficiently fill in defects. Also the use of bone marrow cells for cartilage reconstruction only creates mechanically inferior fibrous cartilage (Pridie drillings, microfracture, AMIC). Presently only cultivated, autologous chondrocytes from the lab are available for a biomechanically high-quality reconstruction of the cartilage layer.The application of mesenchymal stem cells is a subject of extensive international research. However, the first experimental studies, after initial formation of cartilage, disappointingly show significant ossification. Essential conditions for a successful treatment of patellofemoral cartilage damage are the diagnosis of accompanying pathological conditions, selection of the right cartilage-regenerating procedure, sufficient removal of the basic pathological defect, and implementation of standardized rehabilitation.

Marrow stimulation techniques.

Due to the very low intrinsic activity of human adult cartilage, healing of chondral and osteochondral defects in patients cannot be expected. In treating symptomatic cartilage damage, marrow stimulation methods belong to the most frequently used methods, along with autologous chondrocyte transplantation (ACT) and mosaicplasty. These arthroscopic procedures are generally easy and the marrow stimulation treatment costs relatively little. In recent years, Pridie drilling has been increasingly replaced by the microfracture technique. This modification relies on the same biological principles of promoting resurfacing with the formation of fibro-cartilaginous repair tissue. For the treatment of smaller cartilage defects (<2.5 cm(2)), microfracture still remains the first choice for treatment. The clinical results after microfracture in the knee are age dependent. Younger and active patients (<40 years) with smaller isolated traumatic lesions on the femoral condyles have the best long-term results. The deterioration of the clinical results begins after 18 months and is significantly more pronounced in older patients with defects on the patella-femoral joint and tibia. The inferior quality of the repair tissue, partially incomplete defect filling and new bone formation in the defect area seem to be limitations of these methods. The AMIC (autologous matrix induced chondrogenesis) technique was developed to enable treatment of larger defects by the application of a collagen Type III/I membrane (Geistlich Pharma, Wolhusen, Switzerland), in particular when cell-engaged procedures such as ACT cannot be used for financial reasons or because it is not indicated. AMIC seems to be particularly suitable for treating damaged retropatellar cartilage, which is an advantage because these defects can be hard to treat with standard microfracturing alone. The results of the ongoing studies are awaited to establish whether better results with this technology are achievable in the long term.

Results after microfracture of full-thickness chondral defects in different compartments in the knee.

OBJECTIVE: To determine if the clinical results after microfracture of full-thickness cartilage lesions deteriorate over a period of 36 months. METHODS: Between 1999 and 2002 85 patients (mean age 39.5 years) with full-thickness cartilage lesions underwent the microfracture procedure and were evaluated preoperatively and 6, 18 and 36 months after surgery. Exclusion criteria were meniscal pathologies, axial malpositioning and ligament instabilities. Baseline clinical scores were compared with follow-up data by paired Wilcoxon-tests for the modified Cincinnati knee and the International Cartilage Repair Society (ICRS)-score. The effects of the lesion localization and Magnetic resonance imaging (MRI) parameters were evaluated using the Pearson correlation and independent samples tests. RESULTS: Both scores revealed significant improvement 18 months after microfracture (P<0.0001). Within the second 18 months after surgery there was a significant deterioration in the ICRS-score (P<0.0001). The best results could be observed in chondral lesions of the femoral condyles. Defects in other areas of the knee deteriorated between 18 and 36 months after microfracture. MRI 36 months after surgery revealed best defect filling in lesions on the femoral condyles with significant difference in the other areas (P<0.02). The Pearson coefficient of correlation between defect filling and ICRS-score was 0.84 and significant at the 0.01 level. CONCLUSIONS: Microfracture is a minimal invasive method with good short-term results in the treatment of small cartilage defects. A deterioration of the results starts 18 months after surgery and is most evident in the ICRS-score. The best prognostic factors have young patients with defects on the femoral condyles.

[Combinations of different cartilage resurfacing techniques]. / Kombinationen moderner knorpelrekonstruktiver Verfahren.

AIM: The aim of this work was to control the results after simultaneous use of different modern resurfacing techniques. METHODS: We examined the patients who were subjected to different cartilage repair methods using the ICRS score (anterograde drilling, autologous chondrocytes transplantation, OATS, refixation with resorbable pins, spongious bone grafting, HTO). RESULTS: In two cases the combination of different cartilage regenerative methods in a one-step technique produced a good reconstruction of the joint surface with good clinical outcome. With the implantation of carbon plaques, osteolysis of the spongious bone in combination with an incomplete defect filling can be observed. The therapy must be individual and take the clinical, radiological and intraoperative findings into consideration. CONCLUSION: The combination of different resurfacing techniques may have success only if the biomechanical properties of the joint with axial malpositioning and ligament instabilities are considered and treated as well. New prospects are offered particularly for young patients with extensive cartilage damage and without other therapeutic options.

The operative treatment of full thickness cartilage defects in the knee joint with autologous chondrocyte transplantation.

OBJECTIVE: The high clinical and socio-economical impact of cartilage defects and chondral degeneration is well-known. After trauma or without a known etiology, often young patients suffer from pain and a loss of function leading into a decrease of physical activity and, more severe, into long term disability and unemployment. The clinical use of autologous chondrocyte transplantation was introduced in 1994 reporting the data of a pilot study. The objective of this study is to evaluate the efficacy of this method of surgery. METHODS: Autologous chondrocyte transplantation has been established in our department since 1995 for the treatment of large, full thickness cartilage defects which can be completely covered with hyaline-like cartilage without harming the subchondral bone plate. Our first patients (n=24) all showed Grade IV lesions and an average defect size of 6.27 cm2. All but 4 of the patients had at least 1 cartilage defect related operation on the knee. RESULTS: The patients and the clinicians rating indicated an increase of a modified Cincinnati Knee score from 3.6 point pre-operation to 6.9 points after 6 months and 8.1 points at 12 months on a scale from 1 (bad) to 10 (excellent). These results support the data of an international multicenter study with almost 2000 patients. The 5 year results described by the originate authors are good to excellent in 85%-95% with an adverse event rate of 5%. CONCLUSION: Autologous chondrocyte transplantation has to be considered a safe and effective method for the treatment of large full thickness cartilage defects. Alternative treatments are symptomatical: drilling, abrasion, lavage, chondroplasty, or osteotomies. The short term results are promising but a lot of patients have to be treated for osteoarthritis as a consequence of failure with total joint arthroplasty. Osteochondral transplantations have the disadvantage of limited harvesting sites and the impairment of the subchondral bone plate.

[Clinical and cell biology aspects of autologous chondrocytes transplantation]. / Klinische und zellbiologische Aspekte der autologen Chondrozytenimplantation.Methode, Indikationen und wissenschaftliche Ergebnisse.

The treatment of deep cartilage defects is a challenge for every orthopaedic surgeon. The potential for regeneration of cartilage tissue is minimal and leads to mechanically inferior fibrous tissue. The established techniques induce the growth of fibrous tissue but fail to prevent arthrosis. Autologous chondrocyte transplantation seems to be the most promising therapy concept with clinical relevance to reserves a full thickness cartilage defect with hyaline-like cartilage. Outcome studies with a follow up from 2-10 years show in up to 90 % good and excellent results for defects on the femoral condyle and 70 % for the patella. Mechanical testing of the regenerated cartilage showed almost similar stiffness as nearly normal hyaline cartilage. The available data justify the acceptance of autologous chondrocyte transplantation as a standard procedure for limited indications and well-trained surgeons. Result of already inaugurated studies will show the potential of chondrocyte transplantation to prevent osteoarthritis.