Biomimetic Piezoelectric Periosteum‐Bone Integrated Implant Promotes Bone Defect Repair by Remodeling Osteogenic Microenvironment

Abstract Bone defects caused by trauma, infection, or tumors pose significant clinical challenges, particularly in large defects with poor healing outcomes. Traditional repair methods often fail to address the complex regenerative microenvironment. This study introduces a novel biomimetic piezoelectric periosteum‐bone bilayer implant designed to remodel the osteogenic microenvironment and enhance bone defect repair. The implant comprises an upper electrospun polyvinylidene fluoride‐curcumin‐loaded magnesium metal–organic framework (PVDF‐MOF/Cur, PMC) periosteum scaffold and a lower hydroxyapatite@gelatin methacrylate (HA@GelMA) bone scaffold (PMC+HA@GelMA, PMCG). In the whole PMCG bilayer implant, the upper PMC periosteum scaffold improves the piezoelectric properties of PVDF and enables sustained drug release via Mg‐MOF loaded with Cur. Meanwhile, the lower HA@GelMA scaffold facilitates bone marrow mesenchymal stem cells osteogenic differentiation and bone regeneration. Additionally, the upper PMC scaffold further accelerates bone repair by promoting neuronal differentiation, as well as enhancing angiogenesis and regulating macrophage polarization. Transcriptome sequencing reveals that the implant activates key signaling pathways associated with angiogenesis, neurogenesis, inflammation regulation, and osteogenesis, including HIF‐1α, PI3K‐Akt, JAK‐STAT, and TGF‐β pathways. Thus, this work highlights the multifunctional capabilities of the biomimetic periosteum‐bone bilayer implant to remodify the osteogenic microenvironment to accelerate bone defect repair, which offers a promising platform for advancing tissue repair.