The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48 h post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents.

生物力学刺激或机械转导在正常骨稳态和修复中的作用被认为可促进间充质干细胞 (MSC) 在体外的有效成骨。力转导已被整合到多种体外骨组织工程策略中，并提供了控制细胞行为以获得治疗结果的有效方法。然而，植入后向外源性 MSC 群体传递机械刺激构成了重大的转化障碍。在这里，我们描述了一种创新的生物磁性策略 MICA，其中磁性纳米颗粒 (MNP) 用于远程向机械受体 TREK-1 传递机械刺激，从而通过外部磁性阵列产生激活和下游信号传导。在这些研究中，我们将 MICA 转化为临床前绵羊骨损伤模型，以评估功能性骨修复。我们描述了能够进行体内 MNP 操作以及随后在体外等效场强下成骨的磁性阵列的开发。我们进一步证明，MICA 激活的 MSC 在植入后 48 小时体内的活力不受影响。我们提供的证据支持与内部对照相比，个体内 MICA 激活缺陷的早期加速修复和初步增强的骨生长。体外评估了供体对 MICA 激活反应的变异性，结果表明成骨潜力较差的供体通过 MICA 激活得到了最大程度的改善。我们的结果证明了 MICA 体外和体内反应者之间存在明显的关系。这些独特的实验为基于细胞的疗法提供了令人兴奋的临床应用，作为在没有药物制剂的情况下实时动态加载的实际体内来源。