Progranulin-loaded silk fibroin/chitosan scaffold with polydopamine modification promotes bone regeneration via PI3K/Akt pathway activation

Oct 2, 2025International journal of biological macromolecules

Bone healing promoted by a protein-loaded silk and chitosan scaffold with surface coating through activation of a cell growth pathway

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

The SF/CS-PDA@PGRN scaffold led to robust new bone formation in a rat calvarial defect model.

The multifunctional scaffold combines silk fibroin/chitosan with polydopamine and sustained delivery of Progranulin.
In vitro, the scaffold improved adhesion, proliferation, and differentiation of rat bone marrow stem cells.
Transcriptomic analysis indicated that the scaffold's osteoinductive effect may involve activation of the PI3K/Akt pathway.
The design integrates mechanical stability, enhanced surface bioactivity, and long-term biochemical stimulation.
Results suggest a mechanistic connection between molecular regulation and bone regeneration at the animal level.

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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.

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Progranulin-loaded silk fibroin/chitosan scaffold with polydopamine modification promotes bone regeneration via PI3K/Akt pathway activation

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