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Degradation rate affords a dynamic cue to regulate stem cells beyond varied matrix stiffness
Biomaterials ( IF 14.0 ) Pub Date : 2018-04-12 , DOI: 10.1016/j.biomaterials.2018.04.021
Yuanmeng Peng , Qiong-Jie Liu , Tianlei He , Kai Ye , Xiang Yao , Jiandong Ding

While various static cues such as matrix stiffness have been known to regulate stem cell differentiation, it is unclear whether or not dynamic cues such as degradation rate along with the change of material chemistry can influence cell behaviors beyond simple integration of static cues such as decreased matrix stiffness. The present research is aimed at examining effects of degradation rates on adhesion and differentiation of mesenchymal stem cells (MSCs) in vitro on well-defined synthetic hydrogel surfaces. Therefore, we synthesized macromers by extending both ends of poly(ethylene glycol) (PEG) with oligo(lactic acid) and then acryloyl, and the corresponding hydrogels that were obtained after photopolymerization of the macromers were biodegradable. Combining the unique techniques of block copolymer micelle nanolithography with transfer lithography, we prepared a nanoarray of cell-adhesive arginine-glycine-aspartate peptides on this nonfouling biodegradable hydrogel. The biodegradation is caused by hydrolysis of the ester bonds, and different degradation rates in the cell culture medium were achieved by different stages of accelerated pre-hydrolysis in an acidic medium. For the following cell culture and induction, both the matrix stiffness and degradation rate varied among the examined groups. While adipogenic differentiation of MSCs can be understood by the lowered stiffness, the osteogenic differentiation was contradictory with common sense because we found enhanced osteogenesis on soft hydrogels. Higher degradation rates were suggested to account for this interesting phenomenon in the sole osteogenic/adipogenic induction and even more complicated trends in the co-induction. Hence, the degradation rate is a dynamic cue influencing cell behaviors, which should be paid attention to for degradable biomaterials.



中文翻译:

降解速率为调节干细胞提供了动态提示,使其不仅具有变化的基质刚度

尽管已知各种静态线索(例如基质刚度)可调节干细胞的分化,但尚不清楚动态线索(例如降解率以及材料化学变化)是否会影响细胞行为,而不仅仅是静态线索(例如减少的基质)的简单整合刚性。本研究旨在研究体外降解速率对间充质干细胞(MSCs)黏附和分化的影响在明确定义的合成水凝胶表面上。因此,我们通过将聚(乙二醇)(PEG)的两个末端分别与低聚乳酸和丙烯酰进行合成来合成大分子单体,并且大分子单体的光聚合后得到的相应水凝胶是可生物降解的。结合嵌段共聚物胶束纳米光刻技术与转移光刻技术的独特技术,我们在这种不积垢的可生物降解水凝胶上制备了细胞粘附性精氨酸-甘氨酸-天冬氨酸肽的纳米阵列。生物降解是由酯键的水解引起的,并且通过在酸性介质中加速预水解的不同阶段来实现细胞培养基中的不同降解速率。对于随后的细胞培养和诱导,所检查的组之间的基质刚度和降解速率均不同。虽然可以通过降低刚度来了解MSC的成脂分化,但成骨分化与常识相矛盾,因为我们发现软水凝胶增强了成骨作用。有人提出更高的降解率是唯一的成骨/成脂诱导中这种有趣现象的原因,甚至是共诱导中更为复杂的趋势的原因。因此,降解速率是影响细胞行为的动态提示,可降解生物材料应引起注意。有人提出更高的降解率是唯一的成骨/成脂诱导中这种有趣现象的原因,甚至是共诱导中更为复杂的趋势。因此,降解速率是影响细胞行为的动态提示,可降解生物材料应引起注意。有人提出更高的降解率是唯一的成骨/成脂诱导中这种有趣现象的原因,甚至是共诱导中更为复杂的趋势。因此,降解速率是影响细胞行为的动态提示,可降解生物材料应引起注意。

更新日期:2018-07-14
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