The combined effects of matrix stiffness and growth factor immobilization on the bioactivity and differentiation capabilities of adipose-derived stem cells.
The combined effects of matrix stiffness and growth factor immobilization on the bioactivity and differentiation capabilities of adipose-derived stem cells.
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DOI：
10.1016/j.biomaterials.2014.07.012
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发表时间：
2014-10
期刊：
影响因子：
14
通讯作者：
Bailey, Ryan C.
中科院分区：
文献类型：
--
作者：
Banks, Jessica M.;Mozdzen, Laura C.;Harley, Brendan A. C.;Bailey, Ryan C.
关键词：
生物材料设计越来越多地纳入多种指导性信号以诱导预期的细胞反应。然而，许多方法不允许对固定化生长因子信号和基质刚度进行正交操作。此外，很少有方法能以空间选择性的方式支持生物分子信号在生物材料上的图案化。在此，我们报道了一种顺序方法，利用碳二亚胺交联和二苯甲酮光固定化学来正交地改变一种胶原蛋白 - 糖胺聚糖（CG）模型生物材料的刚度和固定化生长因子含量。我们随后研究了骨形态发生蛋白（BMP - 2）、血小板衍生生长因子（PDGF - BB）以及CG膜刚度对脂肪来源干细胞的生物活性以及成骨/成脂谱系特异性基因表达的单独和联合影响，脂肪来源干细胞是再生医学研究中日益受欢迎的细胞来源。我们发现，无论是否存在生长因子，最硬的基质都会引导脂肪来源干细胞（ASCs）向成骨谱系分化，而较软的基质则需要生化信号来引导细胞命运。我们随后描述了使用这种方法在单个基质上创建生长因子的重叠图案。这些结果强调了需要通用的方法来选择性地操纵生物材料微环境，以确定生化和机械信号之间的协同作用，用于一系列再生医学应用。
Biomaterial designs are increasingly incorporating multiple instructive signals to induce a desired cell response. However, many approaches do not allow orthogonal manipulation of immobilized growth factor signals and matrix stiffness. Further, few methods support patterning of biomolecular signals across a biomaterial in a spatially-selective manner. Here, we report a sequential approach employing carbodiimide crosslinking and benzophenone photoimmobilization chemistries to orthogonally modify the stiffness and immobilized growth factor content of a model collagen-GAG (CG) biomaterial. We subsequently examined the singular and combined effects of bone morphogenetic protein (BMP-2), platelet derived growth factor (PDGF-BB), and CG membrane stiffness on the bioactivity and osteogenic/adipogenic lineage-specific gene expression of adipose derived stem cells, an increasingly popular cell source for regenerative medicine studies. We found that the stiffest substrates direct osteogenic lineage commitment of ASCs regardless of the presence or absence of growth factors, while softer substrates require biochemical cues to direct cell fate. We subsequently describe the use of this approach to create overlapping patterns of growth factors across a single substrate. These results highlight the need for versatile approaches to selectively manipulate the biomaterial microenvironment to identify synergies between biochemical and mechanical cues for a range of regenerative medicine applications.
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影响因子：
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作者：
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通讯作者：
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