Cartilaginous tissues can be formed by culturing chondrocytes in three-dimensional cultures in vitro. However, the biochemical and biomechanical properties of these tissues are generally lower than those of articular cartilage. Mechanical stimuli are known to modulate matrix metabolism by articular cartilage explants and metabolic processes in chondrocyte cultures in vitro. However, the effects of perfusion and compression, two such stimuli, on the metabolism of tissue-engineered cartilage have not been fully elucidated. Such physical regulation may be one way of modulating the biochemical and mechanical properties of tissue-engineered constructs. Therefore, these studies examined the effects of perfusion and compression, alone and in combination, on the synthesis and accumulation of matrix proteins in tissue engineered cartilage.
Bovine chondrocytes were seeded onto polyglycolic acid scaffolds and cultured in vitro. The free-swelling growth of these constructs was characterized. The constructs improved in biochemical and mechanical properties during freeswelling culture. However, the properties of the resulting constructs were inferior to those of native cartilage after culture periods of up to six weeks.
Constructs were subjected to perfusion (at fluid velocities of 10μm/sec and 170μm/sec), static compression (at amplitudes of up to 50%), and dynamic compression (at frequencies of 0.001Hz and 0.1Hz and compression offsets of 10% and 50%). Perfusion increased matrix synthesis and cellular content. Static compression suppressed matrix synthesis, while dynamic compression increased matrix synthesis at specific amplitudes and frequencies.
Matched constructs were also subjected to perfusion alone or in combination with dynamic compression for several days. Perfusion increased collagen content in these tissues, while improving the equilibrium compressive modulus of the samples.
These studies show perfusion and compression can modulate the metabolism and accumulation of matrix proteins, as well as the compressive properties of the tissue engineered cartilage. This work provides quantitative information relating the metabolic balance of matrix and cells in tissue engineered cartilage constructs to the physical environment applied during growth. In the future, it is likely that these inputs will be used in optimizing the growth of tissue-engineered cartilage for implantation and repair of articular defects.