A sonoelectric niche for noninvasive intervertebral disc regeneration via targeted cell cycle modulation

作者：Xiaoguang Zhang, Huaizhen Liang, Zhiwei Liao, Bide Tong, Di Wu, Liang Ma, Jie Lei, Xingyu Zhou, Dingchao Zhu, Zixuan Ou, Junyu Wei, Lei Tan, Yang Cao · 发表于：Science Advances · 年份：2025 · DOI：10.1126/sciadv.adu6860 · 被引用次数：8 · 研究领域：Spine and Intervertebral Disc Pathology、Tendon Structure and Treatment、Bone Tissue Engineering Materials

Cell cycle regulation is pivotal for tissue regeneration yet remains challenging in degenerative microenvironments. We engineered a sonosensitive conductive hydrogel incorporating polypyrrole-encapsulated porphyrin derivatives {[Tetrakis (4-carboxyphenyl) porphyrin (TCPP)]@PPy} to regulate cell cycle dynamics. Upon ultrasound irradiation, TCPP@PPy generates free electrons, establishing a controlled microcurrent within degenerative tissues. This sonoelectric niche induces nucleus pulposus cell (NPC) membrane depolarization, activating calcium voltage-gated channels (Ca v ) to drive Ca 2+ influx. Subsequent calcium- and calmodulin-dependent protein kinase I activation up-regulates cyclin-dependent kinases CDK1/CDK2, forming a sonoelectricity–ion–kinase axis that stimulates NPC proliferation and anabolism. Concurrently, ultrasound-responsive borate ester bonds in the hydrogel amplify reactive oxygen species scavenging, counteracting oxidative stress–induced NPC ferroptosis. In a goat model of intervertebral disc degeneration, ultrasound-guided hydrogel implantation alleviated degenerative progression by synergistically reactivating cell cycle progression and suppressing oxidative damage. This strategy demonstrates a noninvasive, dual-targeted approach to regulate degenerative microenvironments through spatiotemporal control of sonoelectric and biochemical cues, offering a translatable strategy for tissue regeneration therapies.