Exosomes derived from hypoxia preconditioned mesenchymal stem cells laden in a silk hydrogel promote cartilage regeneration via the miR-205-5p/PTEN/AKT pathway

Tissue engineering has promising prospects for cartilage regeneration. However, there remains an urgent need to harvest high quality seed cells. Bone marrow mesenchymal cells (BMSCs), and in particular their exosomes, might promote the function of articular chondrocytes (ACs) via paracrine mechanisms. Furthermore, preconditioned BMSCs could provide an enhanced therapeutic effect. BMSCs naturally exist in a relatively hypoxic environment (1%-5% O 2 ); however, they are usually cultured under higher oxygen concentrations (21% O 2 ). Herein, we hypothesized that hypoxia preconditioned exosomes (H-Exos) could improve the quality of ACs and be more conducive to cartilage repair. In our study, we compared the effects of exosomes derived from BMSCs preconditioned with hypoxia and normoxia (N-Exos) on ACs, demonstrating that H-Exos significantly promoted the proliferation, migration, anabolism and antiinflammation effects of ACs. Furthermore, we confirmed that hypoxia preconditioning upregulated the expression of miR-205-5p in H-Exos, suggesting that ACs were promoted via the miR-205-5p/PTEN/AKT pathway. Finally, an injectable silk fibroin (SF) hydrogel containing ACs and H-Exos (SF/ACs/H-Exos) was utilized to repair cartilage defects and effectively promote cartilage regeneration in vivo . The application of SF/ACs/H-Exos hydrogel in cartilage regeneration therefore has promising prospects.