Fig. 2.

TG-18 hydrogel has long-term hydrolytic and encapsulation stability in PBS and exhibits on-demand release of encapsulated TA. a In vitro release kinetics of TA from TG-18 hydrogel in PBS at 37 °C without or with esterase (T. lanuginosus lipase, 200 U/ml). Fresh enzyme was added at the indicated time points (arrows). ***P < 0.001 compared with PBS on day 50. b–d In vitro release kinetics of TA from TG-18 hydrogel in PBS at 37 °C without or with MMP-2 (1.5 µg/ml), MMP-3 (5 µg/ml), or MMP-9 (1 µg/ml). Fresh enzyme or enzyme+MMP inhibitor was added at the indicated time points (arrows). **P < 0.01 compared with PBS or MMP-2 (MMP-9)+inhibitor on day 30 and ****P < 0.0001 compared with PBS or MMP-3+inhibitor on day 25. e In vitro release kinetics of TA in response to synovial fluid from human rheumatoid arthritis joints (SF-RA) and synovial fluid from healthy human joints (SF-healthy). Two hundred microliters of fresh synovial fluid or synovial fluid + MMP inhibitor cocktail were added at the indicated time points (arrows). ****P < 0.0001 and ***P < 0.001 on day 30. P-values were determined by Student’s t-test with Welch’s correction in a and one-way Anova with Tukey’s post hoc analysis in b–e. Data are means ± SD of technical repeats (n = 3, experiments performed at least twice)