Dose-Dependent, Biomechanical Recovery of Permeability Ex Vivo in GAG-Depleted Cartilage With a Synthetic Polyelectrolyte, Polystyrene Sulfonate.

Articular cartilage is a specialized connective tissue responsible for load-bearing function in diarthrodial joints. In early osteoarthritis (OA), depletion of negatively charged glycosaminoglycans (GAGs) side chains within cartilage reduces its ability to maintain high osmotic pressure, leaving the matrix susceptible to further damage. In the biomechanical recovery of damaged cartilage, some OA therapies have focused on collagen repair to restore tissue stiffness, but comparatively fewer have targeted the osmotic contribution of GAGs to cartilage mechanics. In this study, we have investigated poly(styrene) sulfonate (PSS) as a synthetic proteoglycan mimic to restore lost negative charge in GAG-depleted cartilage. Notably, PSS treatment led to near complete recovery of tissue permeability, a direct measure of fixed charge density. In contrast, other commercially available treatments tested did not show measurable biomechanical improvements. These findings, combined with tissue cytotoxicity experiments, demonstrate that PSS-based molecules as synthetic GAG replacements are effective in restoring lost fixed charge density (FCD) and subsequent biomechanical properties of cartilage, thus supporting the potential of PSS as a novel therapeutic strategy for OA.