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Browsing by Author "Zhang, Yu Shrike"

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    Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform
    Skardal, Aleksander; Murphy, Sean V.; Devarasetty, Mahesh; Mead, Ivy; Kang, Hyun-Wook; Seol, Young-Joon; Zhang, Yu Shrike; Shin, Su-Ryon; Zhao, Liang; Aleman, Julio; Hall, Adam R.; Shupe, Thomas D.; Kleensang, Andre; Dokmeci, Mehmet R.; Lee, Sang Jin; Jackson, John D.; Yoo, James J.; Hartung, Thomas; Khademhosseini, Ali; Soker, Shay; Bishop, Colin E.; Atala, Anthony (Springer Nature, 2017-08-18)
    Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases -before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.
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    Programmable microbial ink for 3D printing of living materials produced from genetically engineered protein nanofibers
    Duraj-Thatte, Anna M.; Manjula-Basavanna, Avinash; Rutledge, Jarod; Xia, Jing; Hassan, Shabir; Sourlis, Arjirios; Rubio, Andres G.; Lesha, Ami; Zenkl, Michael; Kan, Anton; Weitz, David A.; Zhang, Yu Shrike; Joshi, Neel S. (Nature Portfolio, 2021-11-23)
    Living cells have the capability to synthesize molecular components and precisely assemble them from the nanoscale to build macroscopic living functional architectures under ambient conditions. The emerging field of living materials has leveraged microbial engineering to produce materials for various applications but building 3D structures in arbitrary patterns and shapes has been a major challenge. Here we set out to develop a bioink, termed as "microbial ink" that is produced entirely from genetically engineered microbial cells, programmed to perform a bottom-up, hierarchical self-assembly of protein monomers into nanofibers, and further into nanofiber networks that comprise extrudable hydrogels. We further demonstrate the 3D printing of functional living materials by embedding programmed Escherichia coli (E. coli) cells and nanofibers into microbial ink, which can sequester toxic moieties, release biologics, and regulate its own cell growth through the chemical induction of rationally designed genetic circuits. In this work, we present the advanced capabilities of nanobiotechnology and living materials technology to 3D-print functional living architectures. Living cells can precisely assemble to build 3D functional architectures. Here the authors produce an extrudable microbial ink entirely from the engineered cells, which can be further programmed to 3D print functional living materials.