Integrating Organs-on-Chips: Multiplexing, Scaling, Vascularization, and Innervation

Park, Do Yeun; Lee, Jaeseo; Chung, Justin J.; Jung, Youngmee; Kim, Soo Hyun

doi:10.1016/j.tibtech.2019.06.006

Cited by 79 publications

(48 citation statements)

References 128 publications

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“…The functional coupling of OOAC models imposes several important design considerations regarding metabolic profiling. The first consideration is related to the metabolic rate and biochemical activity of each OOAC model that is to be coupled with other OOAC models in order to maintain the physiological relevance of analytical results for normal and disease-specific models [41][42][43][44]. The consumption, metabolic conversion, and secretion of energy and respiration compounds, in addition to other relevant metabolites, are known to vary among different cell sources (i.e., immortalized cell lines, primary cells from donor tissue, human induced pluripotent stem cells), inter-laboratory handling and storage conditions, nutrient availability, and tissue maturity [45][46][47][48][49].…”

Section: Scalingmentioning

confidence: 99%

“…Vascularization of OOAC models offers a way to increase physiological relevance via a specific barrier and transport functionalities, as well as interstitial flow modeling, specialized cell-cell interactions, metastatic models, inflammatory models, and drug-or chemical-mediated toxicity models. Various forms of vascularization have been implemented thus far-from separate endothelial cell-lined fluidic supply channels over bioprinted models to specialized angiogenesis chips [43,[70][71][72][73]. Herland et al [19] recently demonstrated quantitative pharmacokinetic responses to orally administered nicotine and intravenously injected cisplatin inside their interconnected, vascularized organ chips that had been perfused using a common blood surrogate [19].…”

Section: Vascularization and Universal Culture Mediamentioning

confidence: 99%

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Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

et al. 2020

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Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia.

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Section: Scalingmentioning

confidence: 99%

Section: Vascularization and Universal Culture Mediamentioning

confidence: 99%

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

et al. 2020

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“…Scalability is another important issue in the implementation of microfluidic systems for preclinical studies. Mechatronic, mesoscale, and computer mathematical modeling methods are necessary to transfer the scale from in vivo to in vitro models and to preserve the appropriate conditions in an integrated modular system [ 63 ]. Achievements in many areas have contributed to the creation of the OOC system, which, thanks to continuous improvements, becomes a real alternative to in vivo testing.…”

Section: Organs On-a-chipmentioning

confidence: 99%

Novel Strategies in Artificial Organ Development: What Is the Future of Medicine?

Klak¹,

Bryniarski²,

Kowalska³

et al. 2020

Micromachines

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The technology of tissue engineering is a rapidly evolving interdisciplinary field of science that elevates cell-based research from 2D cultures through organoids to whole bionic organs. 3D bioprinting and organ-on-a-chip approaches through generation of three-dimensional cultures at different scales, applied separately or combined, are widely used in basic studies, drug screening and regenerative medicine. They enable analyses of tissue-like conditions that yield much more reliable results than monolayer cell cultures. Annually, millions of animals worldwide are used for preclinical research. Therefore, the rapid assessment of drug efficacy and toxicity in the early stages of preclinical testing can significantly reduce the number of animals, bringing great ethical and financial benefits. In this review, we describe 3D bioprinting techniques and first examples of printed bionic organs. We also present the possibilities of microfluidic systems, based on the latest reports. We demonstrate the pros and cons of both technologies and indicate their use in the future of medicine.

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“…Currently, resin products finer and more precise than conventional ones are contributing to the development of fundamental life science research and pharmaceutical and medical applications, such as cell analysis devices. For example, these so-called microdevices, such as microwell arrays for single-cell manipulation [ 4 , 5 ], microfluidic channels for rapid and high-throughput polymerase chain reaction (PCR) [ 6 , 7 ], and drug testing [ 8 , 9 ], and point-of-care testing (POCT) devices for blood cell analysis [ 10 ], have been studied extensively. Some of these are already commercially available as high-value-added life science/medical products for cell analysis [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Facile Fabrication of Thin-Bottom Round-Well Plates Using the Deformation of PDMS Molds and Their Application for Single-Cell PCR

Yamahira

Heike

2020

Micromachines

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Recently, microdevices made of resins have been strongly supporting cell analysis in a range of fields, from fundamental life science research to medical applications. Many microdevices are fabricated by molding resin to a mold made precisely from rigid materials. However, because dimensional errors in the mold are also accurately printed to the products, the accuracy of the product is limited to less than the accuracy of the rigid mold. Therefore, we hypothesized that if dimensional errors could be self-corrected by elastic molds, microdevices could be facilely fabricated with precision beyond that of molds. In this paper, we report a novel processing strategy in which an elastic mold made of polymethylsiloxane (PDMS) deforms to compensate for the dimensional error on the products. By heat-press molding a polycarbonate plate using a mold that has 384 PDMS convexes with a large dimensional error of height of ± 15.6 µm in standard deviation, a 384-round-well plate with a bottom thickness 13.3 ± 2.3 µm (n = 384) was easily fabricated. Finally, single-cell observation and polymerase chain reactions (PCRs) demonstrated the application of the products made by elastic PDMS molds. Therefore, this processing method is a promising strategy for facile, low-cost, and higher precision microfabrication.

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Integrating Organs-on-Chips: Multiplexing, Scaling, Vascularization, and Innervation

Cited by 79 publications

References 128 publications

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

Novel Strategies in Artificial Organ Development: What Is the Future of Medicine?

Facile Fabrication of Thin-Bottom Round-Well Plates Using the Deformation of PDMS Molds and Their Application for Single-Cell PCR

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