Fibrous Scaffolds Enhanced the Paracrine Signaling of Mesenchymal Stem Cells for Cartilage Regeneration

Secretome profiles of mesenchymal stem cells (MSCs) are reflective of their local microenvironments and exert an impact on the surrounding cells, eliciting regenerative responses that creates an opportunity for exploiting MSCs towards a cell-free therapy for cartilage repair. The conventional method of culturing MSCs on a tissue culture plate does not provide the physiological microenvironment for optimum secretome production. This study explored the potential of fibrous scaffolds with specific surface topographies in influencing the MSC secretome production and in enhancing the functionality of MSCs and chondrocytes for cartilage repair. Conditioned media generated from MSCs cultured on fibrous scaffolds improved secretome yield and profile that promoted migration, proliferation, chondrogenesis, as well as mitigated inflammation and protected chondrocytes from apoptosis. FAK and ERK signaling were identified as the mechanotransduction pathways to modulate the MSC morphology and its secretome production, which highlighted scaffold fiber orientation as a key design parameter to direct cellular behavior of MSCs and enhance its paracrine functions. This study demonstrates that a fibrous culture platform could be a more efficient approach for improving and fine-tuning the repertoire of MSC secretome for articular cartilage regeneration.