Short-term changes in cell and matrix damage following mechanical injury of articular cartilage explants and modelling of microphysical mediators

摘要

The short-term responses of articular cartilage to mechanical injury have important implications for prevention and treatment of degenerative disease. Cell and matrix responses were monitored for 11 days following injurious compression of cartilage in osteochondral explants. Injury was applied as a single ramp compression to 14 MPa peak stress at one of three strain rates: 7 x 10~(-1) , 7 x 10~(-3) or 7 x 10~(-5) s~(-1). Responses were quantified in terms of the appearance of macroscopic matrix cracks, changes in cell viability, and changes in cartilage wet weights. Loading at the highest strain rate resulted in acute cell death near the superficial zone in association with cracks, followed over the 11 days after compression by a gradual increase in cell death and loss of demarcation between matrix zones containing viable versus nonviable cells. In contrast, loading at the lowest strain rate resulted in more severe, nearly full-depth cell death acutely, but with no apparent worsening over the 11 days following compression. Between days 4 and 11, all mechanically injured explants significantly increased in wet weight, suggesting loss of matrix mechanical integrity independent of compression strain rate. Results demonstrate that short-term responses of cartilage depend upon the biomechanical characteristics of injurious loading, and suggest multiple independent pathways of mechanically-induced cell death and matrix degradation. Modifications to an existing fiber-reinforced poroelastic finite element model were introduced and the model was used for data interpretation and identification of microphysical events involved in cell and matrix injury. The model performed reasonably well at the slower strain rates and exhibited some capacity for anticipating the formation of superficial cracks during injurious loading. However, several improvements appear to be necessary before such a model could reliably be used to draw upon in vitro experimental results for prediction of injurious loading situations in vivo.