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新型便携式加载装置实现体外培养胚胎大鼠骨的微机械加载研究

Micromechanical Loading Studies in Ex Vivo Cultured Embryonic Rat Bones Enabled by a Newly Developed Portable Loading Device.

机构信息

Division of Pediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.

KTH MoveAbility Lab, Department of Engineering Mechanics, KTH Royal Institute of Technology, Stockholm, Sweden.

出版信息

Ann Biomed Eng. 2023 Oct;51(10):2229-2236. doi: 10.1007/s10439-023-03258-2. Epub 2023 Jun 14.

Abstract

Mechanical loading has been described as having the potential to affect bone growth. In order to experimentally study the potential clinical applications of mechanical loading as a novel treatment to locally modulate bone growth, there is a need to develop a portable mechanical loading device enabling studies in small bones. Existing devices are bulky and challenging to transfer within and between laboratories and animal facilities, and they do not offer user-friendly mechanical testing across both ex vivo cultured small bones and in vivo animal models. To address this, we developed a portable loading device comprised of a linear actuator fixed within a stainless-steel frame equipped with suitable structures and interfaces. The actuator, along with the supplied control system, can achieve high-precision force control within the desired force and frequency range, allowing various load application scenarios. To validate the functionality of this new device, proof-of-concept studies were performed in ex vivo cultured rat bones of varying sizes. First, very small fetal metatarsal bones were microdissected and exposed to 0.4 N loading applied at 0.77 Hz for 30 s. When bone lengths were measured after 5 days in culture, loaded bones had grown less than unloaded controls (p < 0.05). Next, fetal rat femur bones were periodically exposed to 0.4 N loading at 0.77 Hz while being cultured ex vivo for 12 days. Interestingly, this loading regimen had the opposite effect on bone growth, i.e., loaded femur bones grew significantly more than unloaded controls (p < 0.001). These findings suggest that complex relationships between longitudinal bone growth and mechanical loading can be determined using this device. We conclude that our new portable mechanical loading device allows experimental studies in small bones of varying sizes, which may facilitate further preclinical studies exploring the potential clinical applications of mechanical loading.

摘要

机械加载被描述为具有影响骨生长的潜力。为了实验研究机械加载作为一种新的局部调节骨生长的治疗方法的潜在临床应用,需要开发一种便携式机械加载装置,以能够在小骨中进行研究。现有的设备庞大,在实验室和动物设施之间转移具有挑战性,并且它们不能提供针对离体培养的小骨和体内动物模型的用户友好的机械测试。为了解决这个问题,我们开发了一种由固定在不锈钢框架内的线性致动器组成的便携式加载装置,该装置配备了合适的结构和接口。该致动器以及所提供的控制系统可以在所需的力和频率范围内实现高精度的力控制,从而实现各种负载应用场景。为了验证这种新设备的功能,在不同大小的离体培养的大鼠骨中进行了概念验证研究。首先,对非常小的胎儿跖骨进行微解剖,并在 0.77 Hz 下施加 0.4 N 的负载 30 s。在培养 5 天后测量骨长时,负载骨的生长小于未负载对照(p < 0.05)。接下来,将胎儿大鼠股骨周期性地暴露于 0.4 N 的负载下,在 0.77 Hz 下进行离体培养 12 天。有趣的是,这种加载方案对骨生长产生了相反的影响,即负载股骨骨的生长明显大于未负载对照(p < 0.001)。这些发现表明,使用该设备可以确定纵向骨生长和机械加载之间的复杂关系。我们得出结论,我们的新型便携式机械加载装置允许对不同大小的小骨进行实验研究,这可能有助于进一步探索机械加载的潜在临床应用的临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89fb/10518283/c2fb7caba980/10439_2023_3258_Fig1_HTML.jpg

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