超声激活的压电贴片增强线粒体自噬并协同抗炎以促进创伤性脑损伤后的神经修复
Ultrasound-activated piezoelectric patch enhances mitophagy and synergistic anti-inflammation to promote neurological repair after TBI.
摘要(中文译文)
创伤性脑损伤（TBI）后的线粒体功能障碍是继发性神经元损伤和神经炎症的核心病理驱动因素。线粒体自噬作为关键的线粒体质量控制机制，对于维持神经元稳态和促进损伤修复至关重要。然而，实现对线粒体自噬的时空精准调控并同时调节神经免疫微环境仍是一项重大挑战。在此，我们设计了一种可植入的压电贴片，该贴片经低强度脉冲超声（LIPUS）激活后，可在损伤部位产生可控的局部电信号并直接作用于受损神经元。该贴片主要上调Piezo1敏感性的机械转导，并诱导线粒体钙的短暂升高，从而促进PINK1/Parkin相关的线粒体自噬流增强。这有助于清除受损线粒体、恢复线粒体膜电位并减轻氧化性神经元损伤（凋亡率从30.42%降至11.78%）。同时，该治疗减少了线粒体DNA（mtDNA）泄漏及促炎因子的释放，驱动小胶质细胞向保护性M2表型极化并重塑神经免疫微环境。在TBI小鼠模型中，该协同策略显著抑制了神经元凋亡、减少了脑组织丢失、提高了病灶周围区域的神经元存活率（NeuN平均荧光强度较TBI组增加3.5倍），并减少了胶质瘢痕形成，最终使运动和认知功能获得显著改善。本研究提出了一种基于压电的TBI治疗策略，将线粒体自噬调控与神经免疫重塑相耦合，为中枢神经系统损伤的精准修复提供了材料设计的新思路和潜在的转化途径。
Abstract
Mitochondrial dysfunction following traumatic brain injury (TBI) is a central pathological driver of secondary neuronal damage and neuroinflammation. Mitophagy, a key mitochondrial quality control mechanism, is essential for maintaining neuronal homeostasis and promoting injury repair. However, achieving spatiotemporally precise regulation of mitophagy while simultaneously modulating the neuroimmune microenvironment remains a major challenge. Here, we design an implantable piezoelectric patch that, upon activation by low-intensity pulsed ultrasound (LIPUS), generates controllable local electrical signals at the injury site and directly acts on damaged neurons. The patch predominantly upregulates Piezo1-sensitive mechanotransduction and induces a transient elevation of mitochondrial Ca, thereby contributing to enhanced PINK1/Parkin-associated mitophagy flux. This facilitates the clearance of damaged mitochondria, restores mitochondrial membrane potential, and alleviates oxidative neuronal injury (apoptosis rate reduced from 30.42% to 11.78%). Concurrently, the treatment reduces mitochondrial DNA (mtDNA) leakage and the release of pro-inflammatory factors, driving microglial polarization toward the protective M2 phenotype and remodeling the neuroimmune microenvironment. In a mouse model of TBI, this synergistic strategy significantly suppresses neuronal apoptosis, reduces brain tissue loss, increases neuronal survival in the peri-lesional area (3.5-fold increase in NeuN mean fluorescence intensity compared to the TBI group), and decreases glial scar formation, ultimately leading to substantial improvements in motor and cognitive functions. This study presents a piezoelectric-based strategy for TBI therapy that couples mitophagy regulation with neuroimmune remodeling, offering new insights into materials design and potential translational avenues for precise repair of central nervous system injuries.
如何引用
AMA
Wei Li, Runzhe Huang, Qingyuan Wu, Pengbo Zhou, Dangli Ren, Jingjing Wang, et al. Ultrasound-activated piezoelectric patch enhances mitophagy and synergistic anti-inflammation to promote neurological repair after TBI.. Bioactive materials. 2027; doi:10.1016/j.bioactmat.2026.08.035.
APA
Wei Li, Runzhe Huang, Qingyuan Wu, Pengbo Zhou, Dangli Ren, Jingjing Wang, et al (2027). Ultrasound-activated piezoelectric patch enhances mitophagy and synergistic anti-inflammation to promote neurological repair after TBI.. Bioactive materials. https://doi.org/10.1016/j.bioactmat.2026.08.035
GB/T 7714
Wei Li, Runzhe Huang, Qingyuan Wu, Pengbo Zhou, Dangli Ren, Jingjing Wang, et al. Ultrasound-activated piezoelectric patch enhances mitophagy and synergistic anti-inflammation to promote neurological repair after TBI.[J]. Bioactive materials, 2027 doi:10.1016/j.bioactmat.2026.08.035.
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