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复杂的磁机械致动促进干细胞组装和软骨生成,用于治疗骨关节炎。

Sophisticated Magneto-Mechanical Actuation Promotes Stem Cell Assembly and Chondrogenesis for Treating Osteoarthritis.

机构信息

Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.

Department of Joint Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Road, Shanghai, 200032, China.

出版信息

ACS Nano. 2023 Nov 14;17(21):21690-21707. doi: 10.1021/acsnano.3c06909. Epub 2023 Oct 20.

Abstract

Abnormal mechanical loading often leads to the progressive degradation of cartilage and causes osteoarthritis (OA). Although multiple mechanoresponsive strategies based on biomaterials have been designed to restore healthy cartilage microenvironments, methods to remotely control the on-demand mechanical forces for cartilage repair pose significant challenges. Here, a magneto-mechanically controlled mesenchymal stem cell (MSC) platform, based on the integration of intercellular mechanical communication and intracellular mechanosignaling processes, is developed for OA treatment. MSCs loaded with antioxidative melanin@FeO magnetic nanoparticles (Magcells) rapidly assemble into highly ordered cell clusters with enhanced cell-cell communication under a time-varying magnetic field, which enables long-term retention and differentiation of Magcells in the articular cavity. Subsequently, via mimicking the gait cycle, chondrogenesis can be further enhanced by the dynamic activation of mechanical signaling processes in Magcells. This sophisticated magneto-mechanical actuation strategy provides a paradigm for developing mechano-therapeutics to repair cartilage in OA treatment.

摘要

异常的机械负荷常常导致软骨的进行性退化,并引发骨关节炎(OA)。尽管已经设计了多种基于生物材料的机械响应策略来恢复健康的软骨微环境,但远程控制用于软骨修复的按需机械力的方法仍然具有挑战性。在这里,我们开发了一种基于细胞间机械通讯和细胞内机械信号转导过程整合的磁控间充质干细胞(MSC)平台,用于 OA 的治疗。负载抗氧化黑素@FeO 磁性纳米颗粒(Magcells)的 MSC 在时变磁场下迅速组装成具有增强细胞间通讯的高度有序细胞簇,这使得 Magcells 能够在关节腔内长期保留和分化。随后,通过模拟步态周期,Magcells 中的机械信号过程的动态激活可以进一步增强软骨生成。这种复杂的磁机械致动策略为开发机械治疗方法修复 OA 中的软骨提供了范例。

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