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一种新型细胞培养动态拉伸系统揭示了提供更好负压伤口治疗的力学生物学机制。

A novel system for dynamic stretching of cell cultures reveals the mechanobiology for delivering better negative pressure wound therapy.

机构信息

The Herbert J. Berman Chair in Vascular Bioengineering, Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, 6997801, Tel Aviv, Israel.

出版信息

Biomech Model Mechanobiol. 2021 Feb;20(1):193-204. doi: 10.1007/s10237-020-01377-6. Epub 2020 Aug 14.

DOI:10.1007/s10237-020-01377-6
PMID:32803464
Abstract

Serious wounds, both chronic and acute (e.g., surgical), are among the most common, expensive and difficult-to-treat health problems. Negative pressure wound therapy (NPWT) is considered a mainstream procedure for treating both wound types. Soft tissue deformation stimuli are the crux of NPWT, enhancing cell proliferation and migration from peri-wound tissues which contributes to healing. We developed a dynamic stretching device (DSD) contained in a miniature incubator for applying controlled deformations to fibroblast wound assays. Prior to the stretching experiments, fibroblasts were seeded in 6-well culture plates with elastic substrata and let to reach confluency. Squashing damage was then induced at the culture centers, and the DSD was activated to deliver stretching regimes that represented common clinical NPWT protocols at two peak strain levels, 0.5% and 3%. Analyses of the normalized maximal migration rate (MMR) data for the collective cell movement revealed that for the 3% strain level, the normalized MMR of cultures subjected to a 0.1 Hz stretch frequency regime was ~ 1.4 times and statistically significantly greater (p < 0.05) than that of the cultures subjected to no-stretch (control) or to static stretch (2nd control). Correspondingly, analysis of the time to gap closure data indicated that the closure time of the wound assays subjected to the 0.1 Hz regime was ~ 30% shorter than that of the cultures subjected to the control regimes (p < 0.05). Other simulated NPWT protocols did not emerge as superior to the controls. The present method and system are a powerful platform for further revealing the mechanobiology of NPWT and for improving this technology.

摘要

严重创伤,包括慢性和急性创伤(例如手术创伤),是最常见、最昂贵和最难治疗的健康问题之一。负压伤口治疗(NPWT)被认为是治疗这两种类型伤口的主流方法。软组织变形刺激是 NPWT 的关键,它可以促进伤口周围组织的细胞增殖和迁移,从而促进愈合。我们开发了一种包含在微型培养箱中的动态拉伸装置(DSD),用于对成纤维细胞伤口分析施加受控变形。在拉伸实验之前,将成纤维细胞接种在具有弹性基底的 6 孔培养板中,使其达到汇合。然后在培养中心诱导挤压损伤,激活 DSD 以施加拉伸方案,这些方案代表了两种常见的临床 NPWT 方案在两个峰值应变水平(0.5%和 3%)下的代表。对集体细胞运动的归一化最大迁移率(MMR)数据进行分析表明,对于 3%的应变水平,在 0.1 Hz 拉伸频率方案下培养的归一化 MMR 约为 1.4 倍,且统计学上显著大于(p < 0.05)未拉伸(对照)或静态拉伸(第二对照)培养的 MMR。相应地,对间隙闭合时间数据的分析表明,接受 0.1 Hz 方案处理的伤口分析的闭合时间比接受对照方案处理的培养物的闭合时间短约 30%(p < 0.05)。其他模拟的 NPWT 方案并没有表现出优于对照方案的优势。本方法和系统是进一步揭示 NPWT 的力学生物学和改进该技术的强大平台。

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