Mesenchymal stem cells (MSCs) are highly sensitive to biomechanics of their extracellular environment. Generally, a higher elasticity of culture substrates can drive cells into the osteogenic lineage, whereas low substrate elasticity results in adipogenesis. Applied mechanical loading by cyclic strain is another major variable influencing cell fate. Yet, little is known about the simultaneous effect of both cues. Therefore, the present study investigated the relative importance of both cues on differentiation. MSCs were cultured in an osteogenic and also an adipogenic environment on soft polyacrylamide (PAAm; E = 23 ± 0.3 kPa), stiff PAAm (111 ± 2 kPa), and polydimethylsiloxane (PDMS; E = 1,5 ± 0.07 MPa) either unstrained or with 8% cyclic strain at 1 Hz. Without strain, the relative expression of the early osteogenic marker alkaline phosphatase (ALP) was significantly higher (78%) on PDMS than on both PAAm. With 8% cyclic strain, ALP expression increased for all groups in comparison with unstrained controls. The highest increase was observed for the soft PAAm by 36%. Moreover, relative oil red O (ORO) expression-indicating adipogenesis-was the highest for unstrained soft PAAm. On the other hand, the percentage of ORO positive cells significantly decreased by 57% and 69% for soft and stiff PAAm when strained. In conclusion, biomaterial elasticity and mechanical loading can act simultaneously on cell differentiation. Substrate elasticity is an important factor, regulating the differentiation, but cyclic strain can drive MSCs towards the osteogenesis even on the softest substrate. As such, the osteogenic effect of mechanical loading can overrule the adipogenic effect of soft substrates, thereby acting as an inhibitor.

中文翻译：

---

机械负荷和基质弹性对间充质干细胞成骨和成脂分化的影响。

间充质干细胞（MSC）对其细胞外环境的生物力学高度敏感。通常，较高的培养底物弹性可以驱动细胞进入成骨细胞系，而较低的底物弹性导致脂肪形成。通过循环应变施加的机械载荷是影响细胞命运的另一个主要变量。然而，关于这两个线索的同时影响知之甚少。因此，本研究调查了这两个线索对分化的相对重要性。MSC在成骨和成脂环境中分别在未拉伸的软聚丙烯酰胺（PAAm; E = 23±0.3 kPa），刚性PAAm（111±2 kPa）和聚二甲基硅氧烷（PDMS; E = 1.5±0.07 MPa）上培养或在1 Hz时具有8％的循环应变。没有压力，早期成骨标记碱性磷酸酶（ALP）在PDMS上的相对表达显着高于（78％）在两个PAAm上。在8％的循环应变下，与未应变的对照组相比，所有组的ALP表达均增加。观察到软PAAm的增幅最高，达36％。此外，相对油红O（ORO）表示脂肪生成的程度对于未拉伸的软PAAm最高。另一方面，应变时，软硬PAAm的ORO阳性细胞百分比显着降低了57％和69％。总之，生物材料的弹性和机械负荷可以同时作用于细胞分化。基质弹性是调节分化的重要因素，但是循环应变甚至可以在最软的基质上驱动MSC趋向成骨。因此，