gms | German Medical Science

Recently, tissue engineering strategies got improved by advances in the understanding of cartilage formation. By complete autologous strategies in vitro cartilaginous tissue is formed that does not question problems like safety, biocompatibility and toxicology. In vitro studies as well as animal studies gave evidence for capability of human chondrocytes to form tissue constructs containing hyaline-specific matrix compounds, signalling molecules and cells, so-called chondrocyte spheroids. Additionally, after contact of chondrocyte spheroids with native cartilage immediate adhesion is followed by integration into native structures and the filling of defects. Using chondrocyte spheroids technology, no additional fixation of the tranplants is necessary. In addition time of surgical can be reduced significantly. Due to absence of xenogenic/synthetic matrix immune response could be avoided. In the presented clinical pilot study completely autologous cultured, human chondrocyte spheroids were transplanted into full thickness cartilage defects of the knee. Repair capacity of chondrocyte spheroids was proven by MRI and clinical assessment.

Human chondrocytes were isolated from cartilage biopsies 5 patients. After short propagation under complete autologous monolayer culture conditions, chondrocytes were allowed to form 3-dimensional aggregates by secretion of and embedding into a de novo synthesised chondrogenic matrix. After 3 to 5 weeks chondrocyte spheroids were transplanted into full thickness cartilage defects of the knee joint. Patients subjective knee conditions, MRI, knee functionality, quality of life and rehabilitation time were evaluated.

Human chondrocytes are capable to synthesize articular cartilage matrix under complete autologous in vitro culture conditions. Resulting chondrocyte spheroids were placed into the prepared defect ground and their immediate specific attachment was mediated by cell-matrix contacts and adhesion of surface chondrocytes to native cartilage. No fibrin glue, no periosteal flap or xenogenic/synthetic matrix/membrane coverage was necessary to keep the already adhered chondrocyte spheroids in place. Surgical time was reduced to only about 45 minutes. Morbidity and patient recovery time were significantly reduced due to minimally invasive surgical treatment. MRI analysis revealed isointense signals of cartilage regenerates.

The positive clinical results of pilot study indicate that chondrocyte spheroids may be an exiting, simple and valuable therapeutic option for the treatment of focal articular cartilage defects.