CO2-assisted drying enhances stability and therapeutic potency of chondrocyte secretome for osteoarthritis

초록

With the growing elderly and obese populations worldwide, the prevalence of knee osteoarthritis (OA) is rising rapidly, affecting over 600 million people. Given that OA lacks effective treatments to halt its progression or regenerate damaged cartilage, there is a pressing need for disease-modifying therapies. In this study, we investigate a chondrocyte-derived secretome as a bioactive therapeutic candidate and focus on optimizing its formulation stability for translational applications. Due to its protein-rich composition, the secretome is inherently unstable in aqueous media, necessitating effective stabilization strategies. To enhance the stability of the chondrocyte secretome, we applied a specialized CO2-assisted drying method-precipitation with compressed fluid anti-solvent (PCA)-and compared its performance to that of conventional lyophilization (LYO). Both methods preserved anti-inflammatory properties; however, PCA-processed secretome demonstrated significantly enhanced anti-catabolic and anabolic activities. These improvements translated into superior therapeutic outcomes in a rat OA model. Our findings highlight the potential of PCA process as a scalable, chemically robust approach for preserving the functionality of protein-based biologics in OA therapy.

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