[Treatment of deep cartilage defects of the knee with autologous chondrocyte transplantation on a hyaluronic Acid ester scaffolds (Hyalograft C)]
The treatment of chondral defects by transplantation of autologous chondrocytes has recently shown further development. Various biomaterials are used as carriers facilitating attachment and even distribution of chondrocytes in the defect. Since 2003 Hyalograft C, hyaluronan-based scaffolds, has been used, in a clinical study, for implantation of autologous chondrocytes in the treatment of deep chondral lesions of the knee at our department.
Eight patients (7 men and 1 woman; average age, 31 years) followed up for at least 9 months were evaluated. The lesions with an average size of 3.9 cm2 were localized on femoral condyles.
The outcome of surgery was evaluated on the basis of the IKDC Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm knee score. The patients underwent MR examination preoperatively and at 3, 6 and 12 months after surgery. The newly-formed cartilage was assessed by International Cartilage Repair Society (ICRS) visual scores at second-look arthroscopy carried out at 9 to 12 months following transplantation. Consistency of the new cartilage developing in the defect and that of healthy cartilage around the defect was compared by means of a special indentation probe in three patients. A biopsy sample was collected from the grafted site for histological, histochemical and immunohistochemical examination.
All patients reported improvement in knee function on average at 10 months after surgery. The average IKDC subjective score increased from 46 points preoperatively to 74 points postoperatively. The KOOS evaluation showed pain relief and improved function. In quality of life evaluation the average score of 35 points before surgery increased to 70 points after it. The average Lysholm knee score was 61 points before and 83 points after surgery. MR findings correlated well with arthroscopic findings. Second-look arthroscopy showed a normal appearance of the newly-formed cartilage in six, and an abnormal appearance in two patients. The average ICRS visual score was 9.4 points. No graft failure was recorded. The newly-produced tissue had the histological characteristics of a mixed hyaline and fibrous cartilage in seven patients, and of hyaline-like cartilage in one patient.
The ICRS visual repair assessment of the newly-formed tissue showed that our results were better than the one-year outcomes reported by Bartlett et al. (11 patients after transplantation of a collagen bilayer seeded with chondrocytes), but worse than the results of an Italian multi-center study (55 patients with Hyalograft C-based grafts followed up on average for 14 months). At almost one year, implantation of on a Hyalograft C resulted in the production of mixed cartilage incorporated well in the subchondral bone. Only one patient had mature hyaline cartilage. One year is too short to allow for complete remodeling of the newly formed cartilage into a mature hyaline cartilage. This is in agreement with other studies suggesting that the new cartilage continues to mature and remodel for a time longer than one year.
Based on our results we suggest that the use of Hyalograft C is a safe and effective option for treatment of deep chondral defects of the knee; it is particularly useful in patients in whom the primary defect treatment has failed. The application of Haylograft C is relatively quick and easy; this is convenient when surgery involves more than one procedure (ligament reconstruction, osteotomy). However, a definite evaluation of this method will be possible only after long-term results are available. Key words: deep cartilage defects, chondral defects, cartilage repair, autologous chondrocyte transplantation, hyaluronan- based scaffold, Hyalograft C, cartilage repair assessment, ICRS.
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- "Cartilage has a limited capacity for self-repair, attributable to its avascular, noninnervated nature, low cell density, and lack of normal tissue repair-associated humoral factors (Hardingham et al. 2002; Heng et al. 2004). Consequently, cell transplantation, such as autologous chondrocyte implantation (ACI), and tissue engineering strategies have been widely studied for cartilage repair (Grande et al. 1989; Brittberg et al. 1994; Burkart and Imhoff 2002; Baums et al. 2006; Podskubka et al. 2006). However, there are three major disadvantages of ACI: (1) chondrocytes are highly differentiated cells, so their proliferative capacities are limited and may continue to decrease with the age of the patient (Dozin et al. 2002), (2) chondrocytes undergo a process of de-differentiation during expansion in monolayer culture (Grundmann et al. 1980; Mallein-Gerin et al. 1990; Nixon et al. 1992), and (3) ACI has been associated with significant donor-site morbidity and changes in some mechanical properties of neighboring articular cartilage has been observed following tissue harvest in an animal model (Lee et al. 2000). "
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ABSTRACT: The repair of articular cartilage injuries is impeded by the avascular and non-innervated nature of cartilage. Transplantation of autologous chondrocytes has a limited ability to augment the repair process due to the highly differentiated state of chondrocytes and the risks of donor-site morbidity. Mesenchymal stem cells can undergo chondrogenesis in the presence of growth factors for cartilage defect repair. Growth and differentiation factor-5 (GDF5) plays an important role in chondrogenesis. In this study, we examined the effects of GDF5 on chondrogenesis of adipose-derived stem cells (ADSCs) and evaluate the chondrogenic potentials of GDF5 genetically engineered ADSCs using an in vitro pellet culture model. Rat ADSCs were grown as pellet cultures and treated with chondrogenic media (CM). Induction of GDF5 by an adenovirus (Ad-GDF5) was compared with exogenous supplementation of GDF5 (100 ng/ml) and transforming growth factor-beta (TGF-beta1; 10 ng/ml). The ADSCs underwent chondrogenic differentiation in response to GDF5 exposure as demonstrated by production of proteoglycan, and up-regulation of collagen II and aggrecan at the protein and mRNA level. The chondrogenic potential of a one-time infection with Ad-GDF5 was weaker than exogenous GDF5, but equal to that of TGF-beta1. Stimulation with growth factors or CM alone induced transient expression of the mRNA for collagen X, indicating a need for optimization of the CM. Our findings indicate that GDF5 is a potent inducer of chondrogenesis in ADSCs, and that ADSCs genetically engineered to express prochondrogenic growth factors, such as GDF5, may be a promising therapeutic cell source for cartilage tissue engineering.
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ABSTRACT: PURPOSE OF THE STUDY The aim of this study was to provide data on the prevalence and epidemiology of isolated deep chondral lesions of the knee, diagnosed in arthroscopy. The study was also aimed to analyse subjective treatment results of localized deep isolated cartilage lesions and to determine how the different factors might affect the final outcome. MATERIAL AND METHODS From 1997 to 2002, 5233 knee arthroscopies were performed. The first part of the study is an epidemiological and statistical analysis of the isolated articular cartilage lesions in which we used the questionnaire based on the International Knee Documentation Committee (IKDC) Questionnaire. The second part is the analysis of subjective treatment evaluation. For this purpose the IKDC criteria were used. Following aspects were taken into account: lesion location and size, time after surgery, patients' age, performed surgical cartilage procedure. The follow-up period ranged from 1 to 7 years. The statistical analysis was performed with the use of the Pearson correlation coefficient and t-test. Significance was set at p<0.05. RESULTS In the analyzed material cartilage lesion was diagnosed in 2931 patients (57.3%). Isolated localized chondral Outerbridge grade 3 and 4 lesions were documented in 5.2% of all patients with diagnosed cartilage lesion. The patellar articular surface (37.5%) and the medial femoral condyle (32.2%) were the most frequent localizations of these lesions. There was no correlation between the results and the period of time after arthroscopy. The best results were obtained in cases of loose body removal, debridement, mosaicplasty and also in cases where the lesion was left untreated. DISCUSSION The management of full-thickness cartilage injury remains one of the most difficult problems in the orthopedic surgery, particularly isolated and symptomatic. In 7 years of follow-up we found good and satisfactory results when debridement and loose body removal was performed and when the lesions was left untreated. Significantly the worst results in subjective evaluation we observed in marrow-stimulating procedures. This study confirms that the appropriate qualification for treatment plays the most important role in successive management of cartilage injuries. CONCLUSIONS Treatment of isolated deep chondral lesions of the knee remains a questionable issue. Little invasive arthroscopic methods as well as using no surgical treatment in grade 3 and 4 isolated cartilage lesions may be effective and improve symptoms and knee function at mid-term follow-up.Our data support also the contention that the natural history of cartilage lesions still remains unpredictable and not well understood.
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