Dual‐Crosslinked Piezoelectric‐Conductive Silk Fibroin Scaffold for Bone Regeneration

ABSTRACT Piezoelectric biomaterials can convert mechanical stimulation into electrical signals to regulate tissue regeneration. However, conventional piezoelectric materials often suffer from brittleness and poor biocompatibility, limiting their biomedical applications. Silk fibroin (SF) is a widely used biomaterial with excellent biocompatibility and mechanical robustness; while its electroactive potential has been successfully harnessed in various fields, the specific application of its intrinsic β‐sheet‐derived piezoelectricity for bone repair remains largely unexplored. We propose a dual‐crosslinking strategy to program piezoelectric functionality within the SF scaffold for bone regeneration. Chemical crosslinking constructs a stable porous microenvironment, while physical crosslinking activates the intrinsic piezoelectricity of the protein network. SF was fabricated into cryogel scaffolds through a chemical crosslinking step, forming a structurally stable porous architecture. Subsequent ethanol treatment induced β‐sheet crystallization, introducing physical crosslinking that increased structural order and encoded piezoelectricity into the scaffold, yielding a piezoelectric SF scaffold (Piezo‐SF). To further enhance electrical signal transmission, a conductive poly(3,4‐ethylenedioxythiophene) (PEDOT) network was introduced to construct a piezoelectric‐conductive scaffold (PiezoC‐SF). Under ultrasound (US) stimulation, the scaffold generated amplified electromechanical signals to significantly enhance bone regeneration in the rat calvarial defect model. This work establishes a bioinspired strategy for programming piezoelectric SF scaffolds through dual crosslinking, providing a promising platform for tissue engineering.