Modulation of Matrix Softness and Interstitial Flow for 3D Cell Culture Using a Cell-Microenvironment-on-a-Chip System

Modulation of Matrix Softness and Interstitial Flow for 3D Cell Culture Using a Cell-Microenvironment-on-a-Chip System
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DOI:
10.1021/acsbiomaterials.6b00379
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发表时间:
2016-11-01
影响因子:
5.8
通讯作者:
Kong, Hyunjoon
Kong, Hyunjoon
中科院分区:
工程技术2区
文献类型:
--
作者:
Clay, Nicholas Edwin;Shin, Kyeonggon;Kong, Hyunjoon

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在过去的几十年中,大量的努力致力于在体外平台内重现体内组织微环境。然而,重新创建具有生理学相关基质性质和流体流动的组织仍然具有挑战性。为此,本研究展示了一种使用细胞微环境芯片(CMOC)平台独立定制基质刚度和间质液流动的方法。胶原蛋白聚乙二醇凝胶定制目前控制刚度和水力传导性制造的微流控芯片。组装芯片以连续产生通过凝胶的稳定介质流。在C-MOC平台中,根据雌激素受体-a(ER-a)、整合素和E-钙粘蛋白的免疫染色分析,间质流减轻了基质柔软性对乳腺癌细胞行为的影响。这种先进的细胞培养平台用于工程组织类似于体外组织,并有助于更好地理解和调节细胞外微环境的生物学作用。
In the past several decades, significant efforts have been devoted to recapitulating the in vivo tissue microenvironment within an in vitro platform. However, it is still challenging to recreate de novo tissue with physiologically relevant matrix properties and fluid flow. To this end, this study demonstrates a method to independently tailor matrix stiffness and interstitial fluid flow using a cell-microenvironment-on-a-chip (CMOC) platform. Collagen-polyethylene glycol gels tailored to present controlled stiffness and hydraulic conductivity were fabricated in a microfluidic chip. The chip was assembled to continuously create a steady flow of media through the gel. In the C-MOC platform, interstitial flow mitigated the effects of matrix softness on breast cancer cell behavior, according to an immunostaining-based analysis of estrogen receptor-a (ER-a), integrin and E-cadherin. This advanced cell culture platform serves to engineer tissue similar to in vitro tissue and contribute to better understanding and regulating of the biological roles of extracellular microenvironments.