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超声刺激下的多功能压电水凝胶通过募集自体干细胞和激活Ca/CaM/CaN信号通路促进软骨形成。

Multifunctional piezoelectric hydrogels under ultrasound stimulation boost chondrogenesis by recruiting autologous stem cells and activating the Ca/CaM/CaN signaling pathway.

作者信息

Liu Yu-Bao, Liu Xu, Li Xiao-Fei, Qiao Liang, Wang Hao-Liang, Dong Yue-Fu, Zhang Feng, Liu Yang, Liu Hao-Yang, Ji Ming-Liang, Li Lan, Jiang Qing, Lu Jun

机构信息

The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Department of Orthopedics, The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, 225009, China.

出版信息

Bioact Mater. 2025 Apr 18;50:344-363. doi: 10.1016/j.bioactmat.2025.04.009. eCollection 2025 Aug.

DOI:10.1016/j.bioactmat.2025.04.009
PMID:40297641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12036080/
Abstract

Articular cartilage, owing to the lack of undifferentiated stem cells after injury, faces significant challenges in reconstruction and repair, making it a major clinical challenge. Therefore, there is an urgent need to design a multifunctional hydrogels capable of recruiting autologous stem cells to achieve cartilage regeneration. Here, our study investigated the potential of a piezoelectric hydrogel (Hyd) for enhancing cartilage regeneration through ultrasound (US) stimulation. Hyd has multiple properties including injectability, self-healing capabilities, and piezoelectric characteristics. These properties synergistically promote stem cell chondrogenesis. The fabrication and characterization of Hyd revealed its excellent biocompatibility, biodegradability, and electromechanical conversion capabilities. and experiments revealed that Hyd, when combined with US stimulation, significantly promotes the recruitment of autologous stem cells and enhances chondrogenesis by generating electrical signals that promote the influx of Ca, activating downstream CaM/CaN signaling pathways and accelerating cartilage formation. An study in a rabbit model of chondral defects revealed that Hyd combined with US treatment significantly improved cartilage regeneration, as evidenced by better integration of the regenerated tissue with the surrounding cartilage, greater collagen type II expression, and improved mechanical properties. The results highlight the potential of Hyd as a novel therapeutic approach for treating cartilage injuries, offering a self-powered, noninvasive, and effective strategy for tissue engineering and regenerative medicine.

摘要

关节软骨由于损伤后缺乏未分化的干细胞,在重建和修复上面临重大挑战,这使其成为一个主要的临床难题。因此,迫切需要设计一种能够募集自体干细胞以实现软骨再生的多功能水凝胶。在此,我们的研究探讨了压电水凝胶(Hyd)通过超声(US)刺激增强软骨再生的潜力。Hyd具有多种特性,包括可注射性、自我修复能力和压电特性。这些特性协同促进干细胞软骨生成。Hyd的制备和表征显示出其优异的生物相容性、生物降解性和机电转换能力。实验表明,Hyd与US刺激相结合时,通过产生促进Ca内流的电信号、激活下游CaM/CaN信号通路并加速软骨形成,显著促进自体干细胞的募集并增强软骨生成。一项在兔软骨缺损模型中的研究表明,Hyd与US治疗相结合显著改善了软骨再生,再生组织与周围软骨的更好整合、更高的II型胶原蛋白表达以及改善的力学性能证明了这一点。结果突出了Hyd作为治疗软骨损伤的一种新型治疗方法的潜力,并为组织工程和再生医学提供了一种自供电、非侵入性且有效的策略。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c035/12036080/a6f854258a03/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c035/12036080/f4c5e14062b2/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c035/12036080/ebc5ef2f7a6b/gr2.jpg
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