Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

Donoghue, Leslie; Nguyen, Khanh; Graham, Caleb; Sethu, Palaniappan

doi:10.3390/mi12020139

Cited by 13 publications

(18 citation statements)

References 189 publications

(213 reference statements)

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“…Although animal studies are considered physiologically relevant, their limited predictability, longer experimentation times, high costs, lack of high-throughput screening associated with the implementation of the 3Rs (reduction, replacement, and refinement) principle, and novel regulations that ban animal experimentation (e.g., in the cosmetics field) led to the need of developing advanced in vitro models [ 149 , 150 , 151 , 152 ]. So, worldwide research groups are dedicating efforts to develop a new generation of advanced in vitro models capable of recapitulating organ functions becoming effective tools for toxicology, pharmacology (investigating drug metabolism, pharmacokinetics, and toxicity), and for the mechanistic understanding of organ physiology and pathophysiology [ 150 , 153 , 154 , 155 ]. Several promising advanced models have been already established with superior physiological relevance, correlation, and validation compared to in vivo models [ 149 , 150 , 151 , 153 , 154 , 156 , 157 , 158 ].…”

Section: Advanced Models For In Vitro Testingmentioning

confidence: 99%

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

et al. 2022

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The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drugs, food, water treatment, and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity, and (epi)genotoxicity. In addition, new technologies, such as organs-on-chips and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of nanomaterials from their production to their final disposal chain is completed using the life cycle assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review, we give an overview of all these elements of nanosafety.

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Section: Advanced Models For In Vitro Testingmentioning

confidence: 99%

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

et al. 2022

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“…microfluidic technology, has enabled the recreation of intricate anatomical features of organs that closely resemble those in vivo in a manner that has not been possible otherwise. In addition, it allowed the design of "plug and play" components that are biologically relevant, simple and easy to use (Donoghue et al, 2021). On the other hand, 3D hydrogels with various extracellular matrix components, coupled with microfluidics, enabled more accurate representations of the cell-cell and cell-environment interactions compared to those in 2D culture plates.…”

Section: Lymph Node On Chip Applicationsmentioning

confidence: 99%

“…Much remains to be done in this field and there are many opportunities to discover the possibilities lymph nodes on-chip can offer (Hwang et al, 2021). Yet, to ensure widespread adoption, it is necessary that the developed lymph node-on-chip platforms are easy to use, relatively inexpensive, and highly reproducible (Donoghue et al, 2021).…”

Section: Future Directionsmentioning

confidence: 99%

Lymph Nodes-On-Chip: Promising Immune Platforms for Pharmacological and Toxicological Applications

et al. 2021

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Organs-on-chip are gaining increasing attention as promising platforms for drug screening and testing applications. However, lymph nodes-on-chip options remain limited although the lymph node is one of the main determinants of the immunotoxicity of newly developed pharmacological drugs. In this review, we describe existing biomimetic lymph nodes-on-chip, their design, and their physiological relevance to pharmacology and shed the light on future directions associated with lymph node-on-chip design and implementation in drug discovery and development.

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“…Three-dimensional multicellular organoids and MPS that combine advances in microfabricated materials, tissue engineering, and cellular biology recapitulate the function of tissues and organs more accurately than standard two-dimensional cell culture tools (Low, L. A., et al 2021). These relatively new technologies have seen a tremendous adoption in the research community over the past decade, with applications in disease modeling (Chan, A., et al 2021, Donoghue, L., 2021, cancer diagnosis (Guo, Q. R., et al 2021), drug safety and toxicity studies (Ma, L., et al 2020, Fowler, S., 2020, Peterson, N. C., et al 2020, and recently SARS-CoV-2 studies (Si, L., et al 2021, Hysenaj, L., et al 2021. Commercial entities such as pharmaceutical, biotechnology, and cosmetic companies are turning to organoids and MPS as they look to develop tools that could help de-risk the development and validate the effectiveness of new products (e.g., therapeutics or cosmetics) (Low, L. A., et al 2021).…”

Section: Organoids and Microphysiological Systemsmentioning

confidence: 99%

Opportunities for Biomanufacturing in Low Earth Orbit: Current Status and Future Directions

Giulianotti¹,

Sharma²,

Clemens³

et al. 2021

Preprint

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In humankind’s endeavor to explore beyond our planet and travel further into space, we are now at the threshold of an era in which it is possible to move to and from low Earth orbit (LEO) with increasing ease and reduced cost. Through the International Space Station (ISS) U.S. National Laboratory, investigators from industry, academia, and government can easily access the unique LEO environment on the ISS to conduct research and development (R&D) activities in ways not possible on Earth. A key advantage of the LEO environment for life sciences research is the ability to conduct experiments in sustained microgravity conditions. The ability to conduct long-term research in microgravity enables opportunities for novel, fundamental studies in tissue engineering and regenerative medicine, including research on stem cell proliferation and differentiation, biofabrication, and disease modeling using microphysiological systems (MPS) that build on prior research using simulated microgravity conditions (Grimm, D., et al. 2018). Over the last decade, space-based research has demonstrated that microgravity informs our knowledge of fundamental biology and accelerates advancements in health care and medical technologies (International Space Station 2019). The benefits provided by conducting biomedical research in LEO may lead to breakthroughs not achievable on Earth. We are now at a transition point, in which nations are changing their approach to space-based R&D. The focus is shifting from government-funded fundamental science toward the expansion of privately funded R&D with terrestrial application and economic value that will drive a robust marketplace for innovation and manufacturing in LEO. Making this long-term transition requires public-private participation and near-term funding to support critical R&D to leverage the benefits of the LEO environment and de-risk space-based research. Studies conducted on the ISS over the past several years have indicated that one area with potential significant economic value and benefit to life on Earth is space-based biomanufacturing, or the use of biological and nonbiological materials to produce commercially relevant biomolecules and biomaterials for use in preclinical, clinical, and therapeutic applications. We must take advantage of the remaining lifetime of the ISS as a valuable LEO platform to demonstrate this economic value and Earth benefit. By facilitating access to the space station, the ISS National Lab is uniquely positioned to enable the R&D necessary to bridge the gap between the initial discovery phase of space-based biomedical research and the development of a sustainable, investment-worthy biomanufacturing market in LEO supported by future commercial platforms. Through a joint effort, the Center for the Advancement of Science in Space (CASIS), which manages the ISS National Lab, and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine brought together thought leaders from around the U.S. for a Biomanufacturing in Space Symposium that consisted of a series of working sessions to review data from past space-based tissue engineering and regenerative medicine research, discuss relevant current space-based R&D in this area, and consider potential future markets to address the questions: What are the most promising opportunities to leverage the ISS to advance space-based biomanufacturing moving forward? What are the current gaps or barriers that, if overcome, could clear pathways toward private investment in LEO as a valued site for research, development, and production activity? And, most importantly: For which opportunities do the most compelling value propositions exist? The goal of the Biomanufacturing in Space Symposium was to help identify the specific areas in which government and industry investment would be most likely to stimulate advancements that overcome barriers. This would lead to a more investment-ready landscape for private interests to enter the market and fuel exponential growth. The symposium was meant to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in space. The symposium identified and prioritized multiple key R&D opportunities to advance space-based biomanufacturing. These opportunities fall in the areas of disease modeling, stem cells and stem-cell-derived products, and biofabrication. Additionally, symposium participants highlighted the critical need for additional data to help validate and de-risk these opportunities and concluded that approaches such as automation, artificial intelligence (AI), and machine learning will be needed to produce and capture the required data. Symposium participants also came to a consensus that public-private partnerships and funding will be needed to advance the opportunities toward a biomanufacturing marketplace in LEO. This paper will summarize the current state of the science and technology on the ISS and in the fields of tissue engineering and regenerative medicine; provide an overview of biomanufacturing R&D in space to date; review the goals of the Biomanufacturing in Space Symposium; highlight the key commercial opportunities and gaps identified during the symposium; provide information on potential market sizes; and briefly discuss the next steps in developing a roadmap to biomanufacturing in space.

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Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

Cited by 13 publications

References 189 publications

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

Lymph Nodes-On-Chip: Promising Immune Platforms for Pharmacological and Toxicological Applications

Opportunities for Biomanufacturing in Low Earth Orbit: Current Status and Future Directions

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