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Systematic Engineering of Intra-Articular Drug Release Profiles Reveals a Key Determinant of Disease-Modifying Efficacy in Post-Traumatic Osteoarthritis

Post-traumatic osteoarthritis (PTOA) is a progressive joint disease for which no disease-modifying osteoarthritis drugs (DMOADs) have been approved. Although injectable drug delivery systems can prolong therapeutic retention within the joint, it remains unclear whether local drug release kinetics influence disease-modifying efficacy. Here, we developed a modular platform of injectable supramolecular hydrogels using biocompatible, generally recognized as safe (GRAS) amphiphilic molecules and...

bioRxiv 7d ago

Leptin Drives Osteoarthritis Pain Through Sensory Neuron Reprogramming Independent of Cartilage Signaling

Objective: Pain in osteoarthritis (OA) is often discordant with structural joint damage, particularly in obesity-associated OA, where adipose-derived signals may drive nociception independently of cartilage pathology. Leptin has been demonstrated to be necessary, but not sufficient, to drive obesity-associated OA. Here, we tested the hypothesis that leptin mediates OA-associated pain through sensory neuron reprogramming rather than chondrocyte-intrinsic signaling, suggesting a fat-sensory...

bioRxiv 1d ago