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通过区域激活雪旺细胞衍生外泌体实现用于神经源性骨再生的声电转换纤维网络

Acousto-Electric Conversion Fiber Networks via Regional Activation of Schwann Cell-Derived Exosomes for Neurogenic Bone Regeneration.

作者信息

Yi Weiwei, Han Xiaoyu, Wang Fan, Tang Qiuyu, Liu Huzhe, Liao Bo, Shen Jieliang, Wang Juan, Cui Wenguo, Bai Dingqun

机构信息

Department of Rehabilitation Medicine, Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Research (Wash D C). 2025 Jul 15;8:0769. doi: 10.34133/research.0769. eCollection 2025.

Abstract

Neurogenic bone regeneration is essential for the effective restoration of bone tissue functionality, with exosomes derived from Schwann cells regionalized in bone injury tissue playing a crucial role in this process. However, precisely regulating the secretion of Schwann cells localized in bone injury tissue to enhance neurogenic bone regeneration remains a considerable challenge. In this study, an injectable, ultrasound-responsive piezoelectric conductive short fiber network (US@SFG) was innovatively developed using uniform short fiber homogenization techniques and multifunctional chemical modifications, enabling precise acoustic-electrical conversion that regionally activated the secretion of miRNAs from Schwann cell-derived exosomes, thereby promoting neurogenic bone regeneration. The incorporation of the piezoelectric polymer glycine imparts superior piezoelectric characteristics to the fiber network, while the conjugated π-electron motion within the conductive graphene network enhances internal electron transfer efficiency, thereby facilitating electrical conductivity. Compared with traditional piezoelectric fiber networks, acousto-electric conversion fiber networks demonstrated a 1.7-fold increase in piezoelectric performance and a 30-fold increase in conductivity, facilitating precise electrochemical regulation under ultrasound stimulation. In vitro studies revealed that acousto-electric conversion fiber networks precisely modulate the secretion of localized Schwann cell exosomal miRNAs (miRNA-494-3p, miRNA-381-3p, and miRNA-369-3p), activating the phosphatidylinositol 3-kinase/protein kinase B and Wnt signaling pathways in bone marrow mesenchymal stem cells, and thereby promoting osteogenic differentiation. Furthermore, in vivo experiments confirmed that under ultrasound imaging guidance, acousto-electric conversion fiber networks could be directed precisely to bone defects, where precise control of ultrasound parameters facilitated acoustic-electrical conversion and electrical signal modulation, markedly promoting the formation of neural networks and bone tissue regeneration. In this study, for the first time, an injectable acousto-electric conversion fiber network was constructed to activate Schwann cell exosomes in bone injury tissue regionally, providing a novel therapeutic strategy and potential molecular targets for neurogenic bone regeneration.

摘要

神经源性骨再生对于有效恢复骨组织功能至关重要,源自施万细胞且定位于骨损伤组织的外泌体在这一过程中发挥着关键作用。然而,精确调控定位于骨损伤组织的施万细胞的分泌以增强神经源性骨再生仍然是一项巨大挑战。在本研究中,利用均匀短纤维均质化技术和多功能化学修饰,创新性地开发了一种可注射的、超声响应性压电导电短纤维网络(US@SFG),实现精确的声电转换,局部激活施万细胞来源外泌体中微小RNA(miRNA)的分泌,从而促进神经源性骨再生。压电聚合物甘氨酸的掺入赋予纤维网络优异的压电特性,而导电石墨烯网络内共轭π电子运动提高了内部电子转移效率,从而促进导电性。与传统压电纤维网络相比,声电转换纤维网络的压电性能提高了1.7倍,电导率提高了30倍,便于在超声刺激下进行精确的电化学调控。体外研究表明,声电转换纤维网络精确调节局部施万细胞外泌体miRNA(miRNA - 494 - 3p、miRNA - 381 - 3p和miRNA - 369 - 3p)的分泌,激活骨髓间充质干细胞中的磷脂酰肌醇3激酶/蛋白激酶B和Wnt信号通路,从而促进成骨分化。此外,体内实验证实,在超声成像引导下,声电转换纤维网络可精确靶向骨缺损部位,精确控制超声参数有助于声电转换和电信号调制,显著促进神经网络形成和骨组织再生。在本研究中,首次构建了一种可注射的声电转换纤维网络,以局部激活骨损伤组织中的施万细胞外泌体,为神经源性骨再生提供了一种新的治疗策略和潜在的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/442e/12260224/de904dae9f9f/research.0769.fig.001.jpg

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