Relative effects of charge shielding by CPCs in healthy and GAG-depleted (OA model) cartilage. (A, B) Predicted swelling pressures for tissues equilibrated with CPC variants, calculated using experimentally observed uptake concentrations in 50% (A) and 90% (B) GAG-depleted bovine articular cartilage explants. (C) Deswelling induced by CPC variants in healthy and GAG-depleted cartilage over a range of intratissue concentrations. To allow for direct comparison of relative deswelling in tissues of different FCD, values were normalized to the swelling pressure of an untreated sample at the respective FCD level (defined as 100% swelling, with intratissue = 0). (D) Normalized deswelling induced by CPC variants following treatment with an equal 30 μM dose, relative to untreated baseline at the respective FCD level (100% swelling or, alternatively, 0% deswelling). FCD, fixed charge density; GAG, glycosaminoglycan; OA, osteoarthritis.