首页> 外文期刊>Acta biomaterialia >Integration of hollow fiber membranes improves nutrient supply in three-dimensional tissue constructs.
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Integration of hollow fiber membranes improves nutrient supply in three-dimensional tissue constructs.

机译:中空纤维膜的整合改善了三维组织构造中的营养供应。

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Sufficient nutrient and oxygen transport is a potent modulator of cell proliferation in in vitro tissue-engineered constructs. The lack of oxygen and culture medium can create a potentially lethal environment and limit cellular metabolic activity and growth. Diffusion through scaffold and multi-cellular tissue typically limits transport in vitro, leading to potential hypoxic regions and reduction in the viable tissue thickness. For the in vitro generation of clinically relevant tissue-engineered grafts, current nutrient diffusion limitations should be addressed. Major approaches to overcoming these include culture with bioreactors, scaffolds with artificial microvasculature, oxygen carriers and pre-vascularization of the engineered tissues. This study focuses on the development and utilization of a new perfusion culture system to provide adequate nutrient delivery to cells within large three-dimensional (3D) scaffolds. Perfusion of oxygenated culture medium through porous hollow fiber (HF) integrated within 3D free form fabricated (FFF) scaffolds is proposed. Mouse pre-myoblast (C2C12) cells cultured on scaffolds of poly(ethylene-oxide-terephthalate)-poly(butylene-terephthalate) block copolymer (300PEOT55PBT45) integrated with porous HF membranes of modified poly(ether-sulfone) (mPES, Gambro GmbH) is used as a model system. Various parameters such as fiber transport properties, fiber spacing within a scaffold and medium flow conditions are optimized. The results show that four HF membranes integrated with the scaffold significantly improve the cell density and cell distribution. This study provides a basis for the development of a new HF perfusion culture methodology to overcome the limitations of nutrient diffusion in the culture of large 3D tissue constructs.
机译:足够的营养和氧气运输是体外组织工程构建体中细胞增殖的有效调节剂。氧气和培养基的缺乏会产生潜在的致命环境,并限制细胞代谢活性和生长。通过支架和多细胞组织的扩散通常会限制体外运输,从而导致潜在的缺氧区域并降低存活组织的厚度。对于体外产生临床相关的组织工程移植物,应解决当前的营养扩散限制。克服这些问题的主要方法包括使用生物反应器培养,具有人工微血管的支架,氧气载体和工程组织的预血管形成。这项研究的重点是开发和利用新的灌注培养系统,以向大型三维(3D)支架内的细胞提供充足的营养。建议通过集成在3D自由形式制造(FFF)支架中的多孔中空纤维(HF)灌注含氧培养基。在聚环氧乙烷-对苯二酸酯-聚对苯二甲酸丁二醇酯嵌段共聚物(300PEOT55PBT45)的支架上培养的小鼠成肌细胞(C2C12),其与改性聚醚醚砜的多孔HF膜(mPES,Gambro GmbH )用作模型系统。优化了各种参数,例如纤维传输特性,支架内的纤维间距和中等流动条件。结果表明,与支架整合在一起的四个HF膜可显着改善细胞密度和细胞分布。这项研究为开发新的HF灌注培养方法以克服大型3D组织构建体中营养物扩散的局限性提供了基础。

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