Journal
BIOTECHNOLOGY JOURNAL
Volume 16, Issue 10, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.202000655
Keywords
biomimetic microplatform; heterotypic coculture; integrated microfluidics; three-dimensional tumor; throughput analysis
Funding
- National Natural Science Foundation of China [31971328, 31470971, 21375106, 31100726]
- Fundamental Research Funds for the Central Universities of the Central South University [202045001]
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This study demonstrates the development of a controllable and steady chemical gradient and heterotypic three-dimensional tumor cocultures for parallel, large-scale analysis of tumor behaviors. The findings highlight the potential applications in oncology, bioengineering, and drug discovery for multifunctional tumor platforms.
Background Cancer has been responsible for a large number of human deaths in the 21st century. Establishing a controllable, biomimetic, and large-scale analytical platform to investigate the tumor-associated pathophysiological and preclinical events, such as oncogenesis and chemotherapy, is necessary. Methods and Results This study presents antitumor investigation in a parallel, large-scale, and tissue-mimicking manner based on well-constructed chemical gradients and heterotypic three-dimensional (3D) tumor cocultures using a multifunction-integrated device. The integrated microfluidic device was engineered to produce a controllable and steady chemical gradient by manipulative optimization. Array-like and size-homogeneous production of heterotypic 3D tumor cocultures with in vivo-like features, including similar tumor-stromal composition and functional phenotypic gradients of metabolic activity and viability, was successfully established. Furthermore, temporal, parallel, and high-throughput analyses of tumor behaviors in different antitumor stimulations were performed in a device based on the integrated operations involving gradient generation and coculture. Conclusion This achievement holds great potential for applications in the establishment of multifunctional tumor platforms to perform tissue-biomimetic neoplastic research and therapy assessment in the fields of oncology, bioengineering, and drug discovery.
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