Abstract
The effects of doxycycline were examined on articular cartilage glycosaminoglycan (GAG) release and biphasic mechanical properties following two levels of impact loading at 1 and 2 weeks postβinjury. Further, treatment for two continuous weeks was compared to treatment for only the 1st week of a 2βweek culture period. Following impact at two levels, articular cartilage explants were cultured for 1 or 2 weeks with 0, 50, or 100 Β΅M doxycycline. Histology, GAG release to the media, and creep indentation biomechanical properties were examined. The βHighβ (2.8 J) impact level had gross surface damage, whereas βLowβ (1.1 J) impact was indiscernible from nonβimpacted controls. GAG staining decreased after High impact, but doxycycline did not visibly affect staining. High impact resulted in decreased aggregate moduli at both 1 and 2 weeks and increased permeability at 2 weeks, but tissue mechanical properties were not affected by doxycycline treatment. At 1 week, High impact resulted in more GAG release compared to nonβimpacted controls. However, following High impact, 100 Β΅M doxycycline reduced cumulative GAG release at 1 and 2 weeks by 30% and 38%, respectively, compared to no treatment. Interestingly, there was no difference in GAG release comparing 2 weeks continuous treatment with 1 week on, 1 week off. These results support the hypothesis that doxycycline can mitigate GAG release from articular cartilage following impact loads. However, doxycycline was unable to prevent the loss of tissue stiffness observed postβimpact, presumably due to initial matrix damage resulting solely from mechanical trauma. Biotechnol. Bioeng. 2008;100: 506β515. Β© 2008 Wiley Periodicals, Inc.