用于脊髓损伤修复中能量代谢重编程的仿生压电水凝胶系统

Biomimetic piezoelectric hydrogel system for energy metabolism reprogramming in spinal cord injury repair.

作者信息

Shi Guoliang, Su Tianqi, Li Junyang, Wang Aoao, Gao Gan, Tao Benzhang, Chen Nantian, Tian Lu, Yan Jun, Zhao Lingzhou, Zhang Jianning, Zhao Yantao

机构信息

Senior Department of Orthopedics, the Fourth Medical Center of PLA General Hospital; Beijing Engineering Research Center of Orthopedics Implants, Beijing, 100048, PR China.

Senior Department of Neurosurgery, the First Medical Center of PLA General Hospital; Medical School of Chinese PLA, Beijing, 100853, PR China.

出版信息

Theranostics. 2025 Mar 31;15(11):4955-4969. doi: 10.7150/thno.108329. eCollection 2025.

Abstract

Spinal cord injury (SCI) leads to limited regenerative capacity and severe energy deficiency in the injury microenvironment. This study aimed to develop a biomimetic piezoelectric hydrogel system that could recapitulate the native tissue microenvironment while enabling wireless physical regulation for SCI repair. A piezoelectric hydrogel was fabricated by integrating KNaNbO (KNN) nanoparticles with porous decellularized spinal cord matrix gel (pDG). The hydrogel's effects on vascular endothelial cell migration, neural stem cell differentiation, and ATP synthesis were evaluated . RNA sequencing was performed to identify key regulatory pathways. The therapeutic efficacy was assessed in a rat model of spinal cord hemisection, examining motor function and angiogenesis. The piezoelectric hydrogel demonstrated excellent biocompatibility and significantly enhanced vascular endothelial cell and neural cell migration. Under ultrasonic stimulation, the hydrogel promoted neural stem cell differentiation into neurons more effectively than control hydrogels. The piezoelectric stimulation increased ATP synthesis and calcium ion flux, activating the Ca2+/Camk2b/PGC-1α signaling axis. studies showed that implantation of the piezoelectric hydrogel combined with ultrasound stimulation significantly improved motor function recovery and promoted angiogenesis. The piezoelectric hydrogel system presents an effective strategy for SCI repair through energy metabolism reprogramming and demonstrates promising potential in neural tissue engineering applications.

摘要

脊髓损伤(SCI)导致损伤微环境中的再生能力受限和严重的能量缺乏。本研究旨在开发一种仿生压电水凝胶系统,该系统能够重现天然组织微环境,同时实现对SCI修复的无线物理调节。通过将铌酸钠钾(KNN)纳米颗粒与多孔脱细胞脊髓基质凝胶(pDG)整合来制备压电水凝胶。评估了该水凝胶对血管内皮细胞迁移、神经干细胞分化和ATP合成的影响。进行RNA测序以确定关键调控途径。在脊髓半横断大鼠模型中评估治疗效果,检查运动功能和血管生成。压电水凝胶表现出优异的生物相容性,并显著增强了血管内皮细胞和神经细胞的迁移。在超声刺激下,该水凝胶比对照水凝胶更有效地促进神经干细胞分化为神经元。压电刺激增加了ATP合成和钙离子通量,激活了Ca2+/Camk2b/PGC-1α信号轴。研究表明,植入压电水凝胶并结合超声刺激可显著改善运动功能恢复并促进血管生成。压电水凝胶系统通过能量代谢重编程为SCI修复提供了一种有效的策略,并在神经组织工程应用中显示出有前景的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/602d/12036890/b9c527054805/thnov15p4955g001.jpg

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