A sequential drug delivery system based on silk fibroin scaffold for effective cartilage repair

Endogenous repair of cartilage defects is a preferential strategy for cartilage repair, but always hindered by insufficient early-stage cells and incomplete cell differentiation at later stages. For in-situ cartilage regeneration, it is crucial to develop a sequential drug release system capable of recruiting endogenous bone marrow mesenchymal stem cells (BMSCs) and promoting their chondrogenic differentiation. Herein, based on our long-term and fruitful research on silk fibroin (SF) porous scaffolds, a cell-free sequential drug delivery SF scaffold was developed. BMSCs affinity peptide PFSSTKT (PFS) was coated on the surface of SF scaffold, in which chondrogenic inducer kartogenin (KGN) and anti-inflammatory factor dexamethasone (DEX) were loaded. PFS was rapidly released within the first 10 days while KGN and DEX could be released over 28 days. The scaffold promoted BMSCs migration and chondrogenic differentiation through the release of PFS and KGN in vitro . Finally, the sequential drug released by the implanted SF scaffolds in rats indeed recruited endogenous BMSCs and significantly promoted the in-situ regeneration of their knee cartilage defects. In summary, this study not only introduces a green and environmentally friendly all silk-based sequential drug delivery system, but also provides an effective tissue engineering functional scaffold for in-situ cartilage regeneration. • Multi-drug loaded silk fibroin scaffold was successfully prepared. • BMSCs affinity peptide, chondrogenic inducer and anti-inflammatory factor were loaded. • The loaded drugs can be sequentially released from silk fibroin scaffold. • The scaffold promoted BMSCs migration and chondrogenic differentiation. • The implanted scaffold showed a significantly promotion of in-situ regeneration cartilage.