Clay Nicholas Edwin, Shin Kyeonggon, Ozcelikkale Altug, Lee Min Kyung, Rich Max H, Kim Dong Hyun, Han Bumsoo, Kong Hyunjoon
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 607 S. Mathews Avenue, 163 Davenport Hall, Urbana, Illinois 61801, United States.
School of Mechanical Engineering, Birck Nanotechnology Center, Purdue University, 585 Purdue Mall, West Lafayette, Indiana 47907, United States.
ACS Biomater Sci Eng. 2016 Nov 14;2(11):1968-1975. doi: 10.1021/acsbiomaterials.6b00379. Epub 2016 Oct 10.
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 (C-MOC) 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-α (ER-α), integrin β1, 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.
在过去几十年里，人们付出了巨大努力在体外平台上重现体内组织微环境。然而，重新创建具有生理相关基质特性和流体流动的全新组织仍然具有挑战性。为此，本研究展示了一种使用芯片上的细胞微环境（C-MOC）平台独立调整基质硬度和间质液流动的方法。在微流控芯片中制备了定制的具有可控硬度和水力传导率的胶原蛋白-聚乙二醇凝胶。组装该芯片以持续产生通过凝胶的稳定培养基流。在C-MOC平台中，根据基于免疫染色的雌激素受体-α（ER-α）、整合素β1和E-钙黏蛋白分析，间质流减轻了基质柔软度对乳腺癌细胞行为的影响。这个先进的细胞培养平台有助于构建类似于体外组织的组织，并有助于更好地理解和调节细胞外微环境的生物学作用。
