Programmed PTH pulsatility coupled with piezoelectric stimulation via ultrasound-activated scaffolds synergizes deep bone defect regeneration

作者：Xin Wang, Lin-Yuan Shu, Bohao Yin, Jianing Ding, Chenjun Liu, Xin Qi, Junjie Guan, Yu‐Wei Ge, Xiaofeng Lian, Hui Sun, Wei Zhang · 发表于：Bioactive Materials · 年份：2025 · DOI：10.1016/j.bioactmat.2025.10.036 · 被引用次数：1 · 研究领域：Bone Tissue Engineering Materials、Ultrasound and Hyperthermia Applications、Planarian Biology and Electrostimulation

Large bone defects in deep anatomical regions continue to pose significant clinical challenges for osteogenic reconstruction. While pulsatile low-dose parathyroid hormone (PTH) administration shows therapeutic potential for bone regeneration, its effective delivery to deep tissue defects remains problematic. To address this limitation, we developed a novel piezoelectric scaffold (KM@PTH) by integrating PTH with potassium sodium niobate (KNN)-mesoporous bioactive glass (MBG) composites. The KM@PTH system achieves synergistic deep bone regeneration by coupling ultrasound-activated piezoelectric stimulation with spatiotemporally programmed PTH pulsatility, where electromechanical microcurrents and biochemical signaling collaboratively enhance osteogenesis. This dual-modality approach initiates electrostatic PTH liberation while ultrasound-induced mechanical vibrations enhance protein release from the scaffold matrix. In a rabbit femoral defect model demonstrating deep tissue penetration capability, ultrasound-triggered pulsatile PTH delivery from KM@PTH significantly enhanced bone regeneration. Transcriptomic profiling identified calcium ion homeostasis as the central regulatory mechanism, elucidating the synergistic interplay between pulsatile PTH kinetics and electromechanical stimulation. The combined modality promoted osteogenesis through coordinated pathways: Enhanced calcium influx stimulating mitochondrial bioenergetics and mineralization; PKA/PKC-mediated upregulation of...