Ultrasound Driven Dual-Layer Piezoelectric Bionic Periosteum Recreating the Periosteal-Bone Interface Microenvironment for Accelerated Bone Regeneration

Abstract

Bone defects combined with extensive periosteal stripping often result in delayed union or non-union, posing a significant challenge in orthopedic surgery. Inspired by the natural periosteum and the physicochemical properties of bone tissue, we developed a novel dual-layer piezoelectric bionic periosteum (DPBP) membrane via electrospinning, aiming to reconstruct the periosteal–bone interface microenvironment and actively promote bone repair. Designed with a hierarchical structure, the DPBP features a dense outer layer serving as a crucial protective barrier, while its biomineralized porous inner layer provides a scaffold for cell attachment. In synergy with ultrasound (US), the inner layer’s piezoelectricity generates endogenous electrical stimulation, promoting stem cell proliferation and osteogenic differentiation by triggering calcium influx and subsequently activating the PI3K/AKT signaling pathway. Furthermore, in vitro studies demonstrated that the DPBP effectively promoted angiogenesis, indicating a synergistic enhancement of osteo-angiogenic coupling. In vivo, in a rat calvarial defect model, the DPBP significantly promoted bone regeneration, enhanced neovascularization, and exhibited beneficial immunomodulatory capabilities. This study presents a bioinspired periosteum substitute that effectively delivers integrated physicochemical signals to actively enhance bone regeneration, offering a promising strategy for challenging clinical applications.

Graphical Abstract

Keywords

Artificial periosteum / Bone regeneration / Piezoelectric biomaterials / Biomimetic materials

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Funding

the National Key Research and Development Program of China(2025ZD0619000)

the Development and Clinical Demonstration of an Innovative Internal Fixation System for Femoral Neck Fractures(2023YFC2508804)

Key R&D Program of the China Ministry of Science and Technology (2024YFC2510600)

Science and Technology Projects of Xizang Autonomous Region(XZ202301ZY0046G)

Sichuan Science and Technology Program(2023NSFSC1753)

Commission of Sichuan Province Medical Science and Technology Program(24QNMP005)

1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University(2023-309)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China