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(4) Furthermore, the oxidative stress imbalance, caused by excessive ROS production, impairs the antioxidant defense system by directly damaging antioxidant enzymes (such as SOD and GPx) and depleting key antioxidant molecules like glutathione, leading to fragmentation of hyaluronic acid in the extracellular matrix and abnormal collagen cross-linking, thereby reducing the mechanical properties of cartilage (6, 22, 23)

doi: 10.3390/ijms23063138 153 ChenRZouJKangRTangD

Table 1 links recurrent TME phenotypes to dominant barriers, design objectives, candidate nanotherapeutic strategies and key translational cautions