Flow-perfusion bioreactor system for engineered breast cancer surrogates to be used in preclinical testing.
Flow-perfusion bioreactor system for engineered breast cancer surrogates to be used in preclinical testing.
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DOI：
10.1002/term.2026
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发表时间：
2017-04
影响因子：
3.3
通讯作者：
Berry JL
中科院分区：
文献类型：
--
作者：
Marshall LE;Goliwas KF;Miller LM;Penman AD;Frost AR;Berry JL
需要比现有的体外和体内动物模型更好地预测癌症治疗的功效、安全性和药代动力学的临床前测试系统。开发体外预测系统的一种方法是更密切地概括人类癌症的细胞和空间复杂性。使用当前体外系统来模拟癌症的一个限制是缺乏适当大的体积来适应这种复杂性随时间的发展。为了解决这一限制，我们设计并构建了一种新型的流动灌注生物反应器系统，该系统可以通过修改现有的微流体装置来支持由多细胞癌症替代物组成的大体积工程组织。该技术的主要特点是三维 (3D) 体积 (1.2 cm3) 的组织厚度比现有微流体系统中使用的组织厚度更大，并且能够灌注该体积，从而能够开发真实的肿瘤几何形状。该结构是通过用细胞外基质（ECM）水凝胶渗透多孔碳泡沫并通过微通道进行工程制造的。碳泡沫在结构上支持水凝胶和微通道的通畅长达 161 小时。当表面涂有戊二醛（碳泡沫）和硝酸（聚二甲基硅氧烷）时，ECM 水凝胶会粘附在碳泡沫和聚二甲基硅氧烷流动室上，其中容纳水凝胶泡沫结构。此外，与没有微通道或灌注的类似制剂相比，在存在灌注微通道的情况下乳腺癌细胞和成纤维细胞的活力更高。因此，流动灌注生物反应器系统支持生理相关的体积和基质环境中的细胞活力。
There is a need for preclinical testing systems that predict the efficacy, safety and pharmacokinetics of cancer therapies better than existing in vitro and in vivo animal models. An approach to the development of predictive in vitro systems is to more closely recapitulate the cellular and spatial complexity of human cancers. One limitation of using current in vitro systems to model cancers is the lack of an appropriately large volume to accommodate the development of this complexity over time. To address this limitation, we have designed and constructed a novel flow–perfusion bioreactor system that can support large-volume, engineered tissue comprised of multicellular cancer surrogates by modifying current microfluidic devices. Key features of this technology are a three-dimensional (3D) volume (1.2 cm3) that has greater tissue thickness than is utilized in existing microfluidic systems and the ability to perfuse the volume, enabling the development of realistic tumour geometry. The constructs were fabricated by infiltrating porous carbon foams with an extracellular matrix (ECM) hydrogel and engineering through-microchannels. The carbon foam structurally supported the hydrogel and microchannel patency for up to 161 h. The ECM hydrogel was shown to adhere to the carbon foam and polydimethylsiloxane flow chamber, which housed the hydrogel–foam construct, when surfaces were coated with glutaraldehyde (carbon foam) and nitric acid (polydimethyl-siloxane). Additionally, the viability of breast cancer cells and fibroblasts was higher in the presence of perfused microchannels in comparison to similar preparations without microchannels or perfusion. Therefore, the flow–perfusion bioreactor system supports cell viability in volume and stromal contexts that are physiologically-relevant.
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影响因子：
11.2
作者：
Hielscher AC;Gerecht S
通讯作者：
Gerecht S
影响因子：
3
作者：
Buchanan, Cara F.;Voigt, Elizabeth E.;Rylander, Marissa Nichole
通讯作者：
Rylander, Marissa Nichole
影响因子：
14
作者：
Carey, Shawn P.;Kraning-Rush, Casey M.;Williams, Rebecca M.;Reinhart-King, Cynthia A.
通讯作者：
Reinhart-King, Cynthia A.
影响因子：
--
作者：
Sukmana I
通讯作者：
Sukmana I
影响因子：
2.8
作者：
Chen, Michael C. W.;Gupta, Madhuja;Cheung, Karen C.
通讯作者：
Cheung, Karen C.