Two-Dimensional Cellular and Three-Dimensional Bio-Printed Skin Models to Screen Topical-Use Compounds for Irritation Potential

Wei, Zhengxi; Li, Xue; Ooka, Masato; Zhang, Li; Song, Min Jae; Huang, Ruili; Kleinstreuer, Nicole; Simeonov, Anton; Xia, Menghang; Ferrer, Marc

doi:10.3389/fbioe.2020.00109

Cited by 29 publications

(20 citation statements)

References 38 publications

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“…Since the greater part of PM research on skin has been done using 2D models, it is interesting though challenging to translate the results into 3D models and even in vivo outcomes. In a recent study, the irritation potency of several compounds, has been compared in both 2D and 3D models [260]. By screening 451 compounds in 2D models, they were able to select 46 compounds that showed cytotoxicity.…”

Section: Future Directionsmentioning

confidence: 99%

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Dijkhoff¹,

Drašler²,

Karakoçak³

et al. 2020

Part Fibre Toxicol

114

116

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Background: Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles. Main text: To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health. Conclusion: Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.

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Section: Future Directionsmentioning

confidence: 99%

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Dijkhoff¹,

Drašler²,

Karakoçak³

et al. 2020

Part Fibre Toxicol

114

116

View full text Add to dashboard Cite

show abstract

“…These include human primary cells and those differentiated from iPSCs; 3D models including spheroids, organoids, and printed tissues; and microphysiological systems (MPS; or “tissue chips”). Multiple components of the NIH as well as dozens of provider companies and a newly organized IQ MPS Affiliate are conducting and supporting research in all these areas, and early results are promising (e.g.., Wei al 33 …”

Section: A Research Agenda For the Next Decade Of Translational Sciencementioning

confidence: 99%

Opportunities and challenges in translational science

Austin

2021

Clinical Translational Sci

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American population remains frustratingly poor overall (4). This failure of translation is not for lack of effort; over $50B are spent on translational efforts in the public and private sectors every year. Opportunities for improvement abound: the cost of developing a new drug is now over $2B, continues to increase faster than inflation, and has increased relentlessly since 1950 despite enormous advances in science (5); the clinical trials process is widely acknowledged to be inefficient (6,7); after a drug or intervention is shown to be useful, its dissemination to all patients who could benefit is slow and variable (8,9), and patient adherence to those interventions remains suboptimal and limits the health benefits of the interventions developed (10). In all, the time required for the end-to-end translational process, from an idea in the lab to a drug or other intervention based on that idea reaching all patients who could benefit, is currently over 20 years, and its success rate is below 1%. Inspiring individual examples of remarkably effective therapies -including enzyme replacement therapies for particular rare diseases, small molecule correctors for cystic fibrosis, PCSK9 inhibitors for elevated cholesterol, and gene therapies for forms of inherited blindness and spinal muscular atrophy -demonstrate what a future therapeutic world might hold. But those successes remain the exceptions, with development times still measured in decades and resulting products having extremely high costs that are arguably unsustainable, and certainly undesirable. And while there have recently been some encouraging signs of improved overall timelines and success rates, productivity (success per unit of effort) and timelines have worsened over the last 40 years, in stark contrast to the remarkable increase in productivity in fundamental research during this time.These divergence have been recognized for some time (11,12), and a variety of efforts have been undertaken to address it. In the private sector, multiple mergers and acquisitions were undertaken in attempt to achieve economies of scale, and the multi-company collaborative TransCelerate Biopharma was formed in 2012 to create platforms for sharing among companies. Public-private partnerships, including the Innovative Medicines Initiative (IMI) in Europe, and the Accelerating Medicines Partnerships (AMP) in the U.S., have produced substantial datasets that are benefitting the entire research ecosystem. In the academic sector, the NIH Roadmap aimed to "redefine the ways that medical research is conducted and, ultimately, how research leads to improvements in health" (13). Among the Roadmap programs were several aimed at the translational divide. The Molecular Libraries Initiative (14) created a robust small molecule assay development, screening, and chemistry probe development capacity in the public sector for the first time, and was remarkably productive during its 10-year lifetime (15). The Clinical and Translational Science Awards (CTSA) program ( 16) has been similarly tra...

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“…In our work with biofabricating full-thickness skin tissues in a 96-well plate to screen for skin irritants, we systematically obtained coefficient of variance (CV) values of 20% when measuring TEER for the wells in the sample field. 41 Additional unpublished in-house data demonstrate that assays with full-thickness skin models of melanoma and cutaneous squamous cell carcinoma assays in 96-well transwell plates, in which fluorescence signal from green fluorescent protein (GFP)-expressing cancer cells is measured by fluorescence microcopy, have Z factors of 0.4–0.6, which are very robust for 3D tissue models.…”

Section: Operationalizing the Use Of 3d Biofabricated Tissues For Drug Screeningmentioning

confidence: 99%

“…Additionally, many biofabricated tissues have barrier functions, which can be measured in a high-throughput manner using noninvasive TEER probes. 41 These functional TEER measurements can be a highly sensitive readout of tissue health and can be an effective primary, quantifiable output for disease models.…”

Section: Operationalizing the Use Of 3d Biofabricated Tissues For Drug Screeningmentioning

confidence: 99%

Operationalizing the Use of Biofabricated Tissue Models as Preclinical Screening Platforms for Drug Discovery and Development

2021

Self Cite

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Two-Dimensional Cellular and Three-Dimensional Bio-Printed Skin Models to Screen Topical-Use Compounds for Irritation Potential

Cited by 29 publications

References 38 publications

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Opportunities and challenges in translational science

Operationalizing the Use of Biofabricated Tissue Models as Preclinical Screening Platforms for Drug Discovery and Development

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