Most bone tissue engineering models fail to demonstrate the complex cellular functions of living bone; therefore, most translational studies on bone tissue are performed in live models. To reduce the need for live models, we developed a stimulated microchip model for monitoring protein secretion during osteogenesis using human mesenchymal stem cells (hMSCs). We established a bone microchip system for monitoring the in vitro differentiation and sensing the secreted proteins of hMSCs under a sinusoidal electromagnetic field (SEMF), which ameliorates bone healing in a biomimetic natural bone matrix. A 3 V-1 Hz SEMF biophysically stimulated osteogenesis by activating ERK-1/2 and promoting phosphorylation of p38 MAPK kinases. Exposure to a 3 V-1 Hz SEMF upregulated the expression of osteogenesis-related genes and enhanced the expression of key osteoregulatory proteins. We identified 23 proteins that were differentially expressed in stimulated human bone marrow mesenchymal stem cell secretomes or were absent in the control groups. Our on-chip stimulation technology is easy to use, versatile, and nondisruptive and should have diverse applications in regenerative medicine and cell-based therapies.

中文翻译：

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在电磁场刺激下通过微芯片装置评估干细胞分泌蛋白的传感潜力

大多数骨组织工程模型无法证明活骨的复杂细胞功能；因此，大多数关于骨组织的转化研究都是在活体模型中进行的。为了减少对活体模型的需求，我们开发了一种受激微芯片模型，用于使用人间充质干细胞 (hMSCs) 监测成骨过程中的蛋白质分泌。我们建立了一个骨微芯片系统来监测体外在正弦电磁场 (SEMF) 下分化和感知 hMSCs 的分泌蛋白，这可以改善仿生天然骨基质中的骨愈合。3 V-1 Hz SEMF 通过激活 ERK-1/2 和促进 p38 MAPK 激酶的磷酸化来生物物理刺激成骨。暴露于 3 V-1 Hz SEMF 上调了成骨相关基因的表达并增强了关键骨调节蛋白的表达。我们鉴定了 23 种蛋白质，它们在受刺激的人骨髓间充质干细胞分泌组中差异表达或在对照组中不存在。我们的片上刺激技术易于使用、用途广泛且无干扰，应在再生医学和基于细胞的疗法中具有多种应用。