Harnessing topographical & biochemical cues to enhance elastogenesis by paediatric cells for cardiovascular tissue engineering applications.
Harnessing topographical & biochemical cues to enhance elastogenesis by paediatric cells for cardiovascular tissue engineering applications.
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DOI：
10.1016/j.bbrc.2019.03.026
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发表时间：
2019
影响因子：
3.1
通讯作者：
T. Flanagan
中科院分区：
文献类型：
--
作者：
I. Woods;A. Black;S. Jockenhoevel;T. Flanagan
具有仿生细胞外基质（ECM）结构（包括成熟的弹性网络）的组织工程血管移植物（TEVG）的开发仍然是生产具有长期功能的移植物的关键挑战。本研究的目的是研究排列纳米纤维基质对新生儿平滑肌细胞 (SMC) ECM 蛋白质合成的影响，并检查这种拓扑线索与转化生长因子 β-1 (TGF-β1)（一种生化弹性促进剂）的综合影响。玻璃盖玻片涂有电纺纤维蛋白原纳米纤维（平均直径<500 nm），具有随机取向或对齐的形貌。将人脐动脉平滑肌细胞 (hUASMC) 在电纺基质上培养 7 和 14 天，添加或不添加 2ng/ml TGF-β1 补充剂。使用免疫组织化学分析 ECM 结构，并使用染料结合测定测量细胞层中分泌的弹性蛋白的数量。对齐的纤维基质诱导种子细胞和细胞合成的 ECM 纤维的定向定向。与在随机定向的基质上培养的细胞相比，在排列的纤维上培养的细胞表现出表型收缩蛋白表达的显着增加，以及细胞层分泌的弹性蛋白含量的增加。研究表明，补充 TGF-β1 可以协同增加在排列的纤维基质上培养的细胞分泌的弹性蛋白（p<0.05）。对齐的纳米纤维支架可用于指导细胞定向、弹性蛋白相关蛋白质合成和细胞表型，因此它们在 TEVG 的开发中具有应用潜力，作为促进弹性纤维形成的多管齐下策略的一部分。
The development of tissue-engineered vascular grafts (TEVGs) with a biomimetic extracellular matrix (ECM) structure, including a mature elastic network, remains a key challenge for the production of grafts with long-term functionality. The aim of this study was to investigate the influence of aligned nanofiber substrates on ECM protein synthesis by neonatal smooth muscle cells (SMCs), and to examine the combined effects of this topographical cue in conjunction with transforming growth factor beta-1 (TGF-β1) - a biochemical elastogenic promoter. Glass coverslips were coated in electrospun fibrinogen nanofibers (average diameter < 500 nm) with either a randomly-orientated or aligned topography. Human umbilical artery smooth muscle cells (hUASMCs) were cultured on the electrospun substrates for 7 and 14 days, with or without a 2 ng/ml TGF-β1 supplement. The ECM structure was analysed using immunohistochemistry and the quantity of secreted elastin in the cell layer was measured using a dye-binding assay.Aligned fiber substrates induced a directed orientation of both the seeded cells and cell-synthesized ECM fibers. Cells cultured on aligned fibers exhibited a significant increase in the expression of phenotypic contractile proteins, as well as increases in the secreted elastin content of the cell layer, compared to cells cultured on randomly-orientated substrates. TGF-β1 supplementation was shown to synergistically increase secreted elastin from cells cultured on aligned fiber substrates (p < 0.05). Aligned nanofiber scaffolds can be used to direct cellular orientation, elastin-related protein synthesis and cell phenotype, and consequently there is potential for their application in the development of TEVGs as part of a multi-pronged strategy to promote elastic fiber formation.
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影响因子：
14
作者：
Park, Jennifer S.;Chu, Julia S.;Tsou, Anchi D.;Diop, Rokhaya;Tang, Zhenyu;Wang, Aijun;Li, Song
通讯作者：
Li, Song
影响因子：
14
作者：
Baker, Brendon M.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.
影响因子：
4
作者：
Hinderer, Svenja;Shen, Nian;Schenke-Layland, Katja
通讯作者：
Schenke-Layland, Katja
影响因子：
14
作者：
Baker, Brendon M.;Nathan, Ashwin S.;Gee, Albert O.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.