Endogenous repair of cartilage defect is often limited by the insufficient cell numbers in the early stage and incomplete cell differentiation in the later stage. Therefore, it is critical to develop a cell-free biological functional scaffold as an alternative strategy to promote cartilage repair. In this study, a novel, cell-free, and all-silk-based sequential drug delivery scaffold was prepared by coating silk fibroin (SF) solution on the surface of SF porous scaffold and loading bone marrow mesenchymal stem cell (BMSCs) affinity peptide PFSSTKT (PFS) and the chondrogenesis-inducing factor kartogenin (KGN). The results indicated that the SF coating showed a rapid release of PFS during the first 7 days, while the SF porous scaffold slowly and continuously released KGN over 30 days, which synergically promoted BMSCs recruitment and cartilage differentiation. Moreover, it was revealed that PFS and KGN had a synergistic effect on promoting the chondrogenesis of BMSCs by up-regulated the expression of ACAN, Sox9, and COL II at both mRNA and protein levels of in vitro. Finally, the results of in vivo study showed that the implanted SF scaffold significantly promoted the in-situ cartilage regeneration of knee defects in rats by sequential PFS/KGN release, and the structure of the newborn cartilage was close to that of the original tissue. In summary, this study not only provides a green and environmentally friendly all-silk drug sustained-release system, but also a functional scaffold for tissue engineering used for cartilage regeneration.

Schematic illustration of the design of SF-PFS-KGN scaffolds with controlled release of drugs for cartilage repair.

Jinrong Yao

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