Engineered dECM-based microsystem promotes cartilage regeneration in osteoarthritis by synergistically enhancing chondrogenesis of BMSCs and anti-inflammatory effect

Abstract

The cartilage defects in osteoarthritis (OA) often result in loss of supporting and cushioning functionalities. Along this line, tissue engineering strategies for microfluidics based on high-precision control capabilities have been developed as promising long-term therapeutic solutions for cartilage regeneration in OA towards implementing anti-inflammatory effects and subsequent chondroprotective regeneration. In this study, an engineered microcarrier comprising composite porous microspheres based on decellularized extracellular matrix (dECM) and poly(lactic-co-glycolic acid) (PLGA) encapsulating icariin (ICA) was fabricated by microfluidic technology. This microcarrier, co-cultured with bone marrow mesenchymal stem cells (BMSCs), was developed as an injectable engineered microsystem for cartilage regeneration in OA. Mechanistically, dECM effectively repaired cartilage defects by inducing the differentiation of encapsulated stem cells to a cartilage phenotype through microenvironmental effects. In addition to enhanced secretion of active anti-inflammatory substances from BMSCs by dECM, the gradual release of ICA from the degraded PLGA PMs synergized anti-inflammatory effects in vivo, resulting in effective cartilage regeneration in OA. In short, the engineered microsystem indicated favorable effects in protecting and repairing cartilage, highlighting their potential as a promising therapeutic intervention for effectively ameliorating OA.