Progranulin-loaded silk fibroin/chitosan scaffold with polydopamine modification promotes bone regeneration via...

Bone defect repair remains a major clinical challenge, as existing bone tissue engineering scaffolds often suffer from insufficient biocompatibility and limited osteogenic activity. Here, we developed a multifunctional scaffold by combining mechanical stability from silk fibroin/chitosan (SF/CS), polydopamine (PDA)-mediated surface modification, and sustained delivery of Progranulin (PGRN). This synergistic design integrates structural support, notably enhanced surface bioactivity, and long-term biochemical stimulation. In vitro, the SF/CS-PDA@PGRN scaffold demonstrated improved rBMSC adhesion, proliferation, and osteogenic differentiation. Transcriptomic profiling, together with pathway inhibition, suggested that its osteoinductive effect was mediated at least in part through activation of the PI3K/Akt pathway. In vivo, implantation in a rat calvarial defect model confirmed robust new bone formation and remodeling. Collectively, these results highlight the scaffold's multi-functional design-mechanical integrity, bioactive surface, and controlled release-while also demonstrating a clear mechanistic link between molecular regulation and animal-level bone regeneration. These findings underscore the translational potential of SF/CS-PDA@PGRN scaffolds as an innovative strategy for bone tissue engineering.