The influence of cell-matrix attachment and matrix development on the micromechanical environment of the chondrocyte in tissue-engineered cartilage.

Insufficiency of mechanical properties of tissue-engineered (TE) cartilage grafts is still a limiting factor for their clinical application. It has been shown that mechanostimulation of chondrocytes enhances synthesis of extracellular matrix (ECM) and thereby improves the mechanical properties of the grafts. However, the optimal mechanical loading required to stimulate chondrocytes for sufficient matrix synthesis is still unknown. The properties of the pericellular matrix (PCM) and the ability of the chondrocytes to attach to its adjacent matrix may importantly determine the stimulation of the cell in loaded tissue. The aim of the present study is to numerically investigate the influence of tissue development and cell-matrix attachment on the mechanical environment of a chondrocyte embedded in agarose. Mechanical environment inside TE constructs is evaluated and compared with that in native cartilage under 10% unconfined compression. A multiscale finite element modeling approach in conjunction with a validated nonlinear fiber-reinforced poroviscoelastic swelling cartilage model is used. Results indicate that without cell attachment, excessive local strains may be induced in the cell. With PCM development and the establishment of focal adhesions at the cell surface, the cell is strained more homogenously upon external loading. However, compared with chondrocytes in native cartilage, the transmission of the external compression to the cells in TE constructs is less. This suggests that, over time, the loading magnitude may be increased to continue stimulation of chondrocytes at the physiological or even higher levels to possibly enhance matrix synthesis. These findings improve our insights into the micromechanical environment of cells in tissue engineering cultures.