Self‐Assemble Silk Fibroin Microcapsules for Cartilage Regeneration through Gene Delivery and Immune Regulation

Abstract Effective treatments for cartilage defects are currently lacking. Gene delivery using proper delivery systems has shown great potential in cartilage regeneration. However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer‐by‐layer self‐assembly, in which interleukin‐4 (IL‐4) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self‐assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL‐4 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk‐based microcapsule delivery system can also provide strategies for the treatment of other diseases.