Repair of cartilage and fibrocartilage in large synovial joints

In large synovial joints, tissues such as cartilage, meniscus/acetabular labrum, subchondral bone and the muscle- capsule-ligament complex constitute a functional unit. All these structures work together to maintain joint homeostasis. Connective tissue lesions are still of major interest to orthopaedic surgeons, because most of these lesions do not heal spontaneously. Biologic factors may play a determining role in successful repair and may be of more importance than the surgical technique. In recent decades, knowledge on hyaline cartilage biology has increased rapidly. In contrast, studies on the metabolism of human meniscus and acetabular labrum cells of the knee and hip joint respectively, are scarce. This work demonstrated that the human acetabular labrum is populated with unique highly active fibrochon- drocyte-like cells. These cells are capable of expressing and releasing pro-inflammatory enzymes and cytokines and react on pro-inflammatroy stimuli. In this way, they obviously contribute to disturbed tissue function in pathology and therefore should be considered as a potential therapeutic target in hip joint disease. In the future, for example, attempts can be made to modulate the behavior of human acetabular labrum cells to promote heal- ing of labral tears. The histologic aspects of human acetabular labrum repair were documented in this thesis. It was shown that human labral tears display healing potential following surgical repair. The surfaces of the labral tissues were intact and neither remainings of the tear or presence of fibrovascular scar tissue were observed. However, some small clefts in the superior and the deep part of the repaired structures were noticed in all cases. In contrast to the acetabular labrum, cartilage does not have a vascular supply. Moreover, postnatal articular chondrocytes display little mitotic activity levels and the articular cartilage extracellular matrix has a low turn- over rate. Therefore, enchondral lesions do not heal spontaneously. In the this thesis, we discuss the outcome of different cartilage repair strategies. We present the outcome of three types of augmented marrow-stimulation techniques and of 2 types of cell-based repair techniques. First, we used a synthetic osteochondral scaffold plug to fill the cartilage defect. Secondly, we combined micro- fracture with a cell-free polymer-based chondrotissue matrix and thirdly, we combined the original AMIC pro- cedure combining a collagen I/III sealing with platelet-rich plasma gel (PRP - AMIC plus). In general, we can conclude that the use of the presented augmented marrow-stimulation techniques is feasible for cartilage repair in the knee. These 1-step procedures show a statisfactory clinical outcome. However, they demonstrate sub- chondral bone changes in most of the cases, even the formation of intralesional osteophytes. Caution is needed when synthetic scaffolds are implanted into the subchondral bone. The resorption process of these materials can take some time and provoke symptoms. In some cases, there is even the need for the removal of these materials. The first cell-based biological approach to treat cartilage lesions was introduced by Brittberg et al. in 1987 and termed autologous chondrocyte implantation (ACI). This technique has gained wide scientific and clinical support for use in the repair of focal articular lesions. However, during in vitro propagation of the chondro- cytes, dedifferentiation of the cells can occur, and afterwards these fibroblast-like chondrocytes show different biosynthetic properties than the original cells in hyaline articular cartilage. We present the outcome of two cell- based approaches that attempt to address the issue of dedifferentiation of cultured chondrocytes. First, we discussed the short-term outcome of the second-generation characterized chondrocyte implantation (CCI) - which uses a collagen I/III membrane to cover the defect - for the treatment of cartilage lesions in the knee. It was concluded that this technique is safe and feasible for the treatment of cartilage defects in the knee and that the overall results are promising. However, no clear beneficial effect of an inert sealing membrane was observed. Another way to avoid the issue of dedifferentiation during in vitro propagation of chondrocytes is the use of instantaneously delivered allogenic chondrocytes. We present in thesis the short- and midterm outcome of our using a biodegradable, alginate-based biocompatible scaffold containing human allogenic chondrocytes for the treatment of cartilage lesions in the knee. The patients treated with this technique exhibited a strong clinical improvement after surgery and this improvement remained quite stable over time. However, the promising clinical outcome was not associated with favorable MRI findings. Longer clinical follow-up will show in how far MR imaging is a proper surrogate marker for clinical improvement. Taken all together, most of the cartilage techniques report favorable outcome at different follow-up times, which was also the case with the presented marrow-stimulation and cell-based techniques presented in this thesis. However, the overall short-term MRI aspect of the subchondral bone was superior with cell-based tech- niques compared to the marrow-stimulation techniques