Wang Wenhan, Li Keyi, Ma Wenjun, Li Yiwei, Liu Feng, Kong Ying, Wang Liang, Yi Fan, Sang Yuanhua, Li Gang, Liu Hong, Qiu Jichuan
State Key Laboratory of Crystal Materials, Shandong University, Jinan, China.
Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Nat Mater. 2025 May 6. doi: 10.1038/s41563-025-02214-w.
Traumatic brain injury (TBI) is associated with life-threatening and permanent disabilities. Given the limited capacity of neurons to regenerate, effective treatments for TBI are lacking. Neural stem cells (NSCs) can differentiate into fully functioning neurons and thus hold promise for TBI treatment. Nonetheless, NSC differentiation and proliferation are slow and inefficient. Studies have shown that piezoelectric stimulation is capable of promoting the differentiation and proliferation of NSCs. Here, we describe barium titanate-reduced graphene oxide (BTO/rGO) hybrid piezoelectric nanostickers that promote NSC proliferation and differentiation. These hybrid nanostickers attach to NSC membranes, serving as long-term generators of piezoelectric potentials upon ultrasound stimulation. BTO/rGO nanostickers promote rapid neuronal differentiation and maturation by activating the voltage-gated calcium channel/Ca/calmodulin-dependent protein kinase II/cAMP response element-binding protein pathways. Transplantation of NSCs with BTO/rGO nanostickers into the injured brain region of rats with TBI substantially repairs brain tissue and effectively restores physiological functions after 28 d following 5-min ultrasound irradiation every 2 d. These results demonstrate the potential of the combination of NSCs and BTO/rGO nanostickers for TBI treatment.
创伤性脑损伤（TBI）与危及生命的永久性残疾相关。鉴于神经元再生能力有限，目前缺乏针对TBI的有效治疗方法。神经干细胞（NSCs）可以分化为功能完全正常的神经元，因此有望用于TBI的治疗。尽管如此，NSC的分化和增殖缓慢且效率低下。研究表明，压电刺激能够促进NSCs的分化和增殖。在此，我们描述了钛酸钡-还原氧化石墨烯（BTO/rGO）混合压电纳米贴片，其可促进NSC的增殖和分化。这些混合纳米贴片附着于NSC膜上，在超声刺激下作为压电电位的长期发生器。BTO/rGO纳米贴片通过激活电压门控钙通道/Ca/钙调蛋白依赖性蛋白激酶II/cAMP反应元件结合蛋白途径促进神经元的快速分化和成熟。将携带BTO/rGO纳米贴片的NSCs移植到TBI大鼠的损伤脑区，每2天进行5分钟的超声照射，28天后可显著修复脑组织并有效恢复生理功能。这些结果证明了NSCs与BTO/rGO纳米贴片联合用于TBI治疗的潜力。
