Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels

Due to its avascular nature, articular cartilage exhibits a very limited ca pacity to regenerate and to repair. Although much of the tissue-engineered cartilage in existence has been successful in mimicking the morphological a nd biochemical appearance of hyaline cartilage, it is generally mechanicall y inferior to the natural tissue. In this study, we tested the hypothesis t hat the application of dynamic deformational loading at physiological strai n levels enhances chondrocyte matrix elaboration in cell-seeded agarose sca ffolds to produce a more functional engineered tissue construct than in fre e swelling controls. A custom-designed bioreactor was used to load cell-see ded agarose disks dynamically in unfolded compression with a peak-to-peak c ompressive strain amplitude of 10 percent, at a frequency of 1 Hz, 3 X (1 h our on, 1 hour off)/day, 5 days/week for 4 weeks. Results demonstrated that dynamically loaded disks yielded a sixfold increase in the equilibrium agg regate modulus over free swelling controls after 28 days of loading (100 +/ - 16 kPa versus 15 +/- 8 kPa, p<0.001). This represented a 21-fold increase over the equilibrium modulus of day 0 (4.8+/-2.3 kPa). Sulfated glycosamin oglycan content was also found to be greater in dynamically loaded disks co mpared to free swelling controls at day 21 (p<0.0001 and p=0.002, respectiv ely).