Microsphere System Coloading Type I Collagen and Dexamethasone Sodium Phosphate for Osteoarthritis Therapy

Abstract Knee osteoarthritis (KOA) has no effective nonsurgical treatment. Intra-articular therapy constitutes an effective localized intervention; however, persistent lymphatic drainage and synovial vascular exchange lead to rapid drug elimination. Encapsulating bioactive agents into microsphere delivery platforms enables localized intra-articular administration, with their scaffold-based spherical architecture serving as pharmaceutical and cellular carriers or tissue engineering scaffolds, representing a highly promising therapeutic avenue for KOA. Herein, PLGA was employed to prepare microspheres and a sustained-release microsphere formulation (MPs PLGA DSP@COLI) was prepared for KOA therapeutics, co-encapsulating type I collagen (COLI) and dexamethasone sodium phosphate (DSP). Characterization revealed uniform particle size distribution, favorable dispersibility, and extended-release kinetics. Functional assessments demonstrated robust anti-inflammatory efficacy and enhanced chondrocyte-mediated extracellular matrix deposition. Histopathological and immunohistochemical analyses demonstrated preserved cartilage matrix integrity, augmented COLII synthesis, diminished inflammatory cellular infiltration, and maintained homeostasis of cartilage matrix components, concomitant with reduced OARSI and synovitis scores. These effects collectively suppressed synovial hyperplasia and inflammation and suggested potential improvement in joint conditions. Overall, MPs PLGA DSP@COLI combines the pharmacological anti-inflammatory properties of DSP with the extracellular matrix-related biological functions of COLI, establishing an innovative “drug-device combination” therapeutic paradigm, which represents a promising therapeutic strategy for KOA.