Article
Biotechnology & Applied Microbiology
Nan Chen, Mieradilijiang Abudupataer, Sisi Feng, Shichao Zhu, Wenrui Ma, Jun Li, Hao Lai, Kai Zhu, Chunsheng Wang
Summary: The study tested metformin using human pluripotent stem cell-derived aortic smooth muscle cells in an in vitro microphysiological system and found that metformin could help restore a contractile phenotype in cells, potentially for treating aortic aneurysms. This research contributes to identifying potential drug targets for the treatment of aortic aneurysms.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Chemistry, Analytical
Huyen Ngo, Sarnai Amartumur, Van Thi Ai Tran, Minh Tran, Yen N. Diep, Hansang Cho, Luke P. Lee
Summary: The advancements in cancer-on-chip technology have allowed for the recapitulation of vital biological features of various cancer types and their applications in life sciences and high-throughput drug screening. However, challenges such as the complexity of the tumor microenvironment and integrating multiple organs still need to be addressed. Integrated biosensors in advanced cancer-on-chip platforms offer high-throughput monitoring of real-time cellular responses for drug development.
Article
Chemistry, Multidisciplinary
Joon Ho Kang, Minjeong Jang, Su Jin Seo, Andrew Choi, Daeeun Shin, Suyoung Seo, Soo Hyun Lee, Hong Nam Kim
Summary: In infectious diseases like sepsis and COVID-19, improving vascular barrier function is crucial. This study shows that osmolarity modulation can effectively enhance vascular barrier function, even in the presence of inflammation. Through the use of 3D human vascular microphysiological systems, it is demonstrated that hyperosmotic exposure for 24-48 hours can significantly improve vascular barrier function, while hypo-osmotic exposure disrupts it. The findings suggest that osmolarity modulation may be a unique therapeutic strategy to protect vascular barrier function and prevent the progression of infectious diseases.
Article
Chemistry, Multidisciplinary
Jeong-Won Choi, Minwook Seo, Kyunghwan Kim, A-Ru Kim, Hakmin Lee, Hyung-Seok Kim, Chun Gwon Park, Seung Woo Cho, Joo H. Kang, Jinmyoung Joo, Tae-Eun Park
Summary: By using a human microphysiological system (MPS)-based SELEX method, a human BBB shuttle aptamer (hBS) with high efficiency in crossing the blood-brain barrier was successfully screened. The hBS demonstrated enhanced uptake efficiency in brain microvascular endothelial cells and brain cells, and showed high specificity and accumulation in the brain.
Article
Chemistry, Multidisciplinary
Arun Asif, Sung Hyuk Park, Afaque Manzoor Soomro, Muhammad Asad Ullah Khalid, Abdul Rahim Chattikatikatuveli Salih, Bohye Kang, Faheem Ahmed, Kyung Hwan Kim, Kyung Hyun Choi
Summary: In the field of microfluidics, microphysiological systems (MPS) are addressing the challenge of physiological relevance in drug discovery and development by integrating a microfluidic albumin immunosensor with liver-on-a-chip MPS.
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Sonia Youhanna, Volker M. Lauschke
Summary: The intestinal epithelium acts as a selective barrier for water, nutrients, and orally administered drugs. Scientists and drug developers use various cell culture models to evaluate the gastrointestinal permeability of candidate molecules. Advanced culture models show potential for emulating intestinal complexity, but there is a lack of systematic absorption studies and benchmarking data to confirm their reliability, leaving conventional static transwell cultures as the current gold standard for drug absorption studies.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Christopher M. Arian, Tomoki Imaoka, Jade Yang, Edward J. Kelly, Kenneth E. Thummel
Summary: The intestine plays a crucial role in the absorption of orally administered drugs, and understanding drug disposition within the intestine is important in drug development. Current in vitro systems provide knowledge about drug absorption and the first-pass effect, but they are not ideal for predicting this process and drug bioavailability. Emerging in vitro systems, such as intestinal organoids and microphysiological systems, show promise in accurately replicating intestinal physiology and biochemistry, and may serve as preclinical testing platforms in the future.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Engineering, Biomedical
Ulgu Arslan, Alessia Moruzzi, Joanna Nowacka, Christine L. Mummery, Dominik Eckardt, Peter Loskill, Valeria V. Orlova
Summary: Models of heart disease and drug responses are shifting towards the use of human pluripotent stem cells (hPSCs) due to their superior ability to capture human heart (dys-)function compared to animal models. However, simple monolayer cultures of hPSC-derived cardiomyocytes have limitations. This review discusses the strategies for overcoming these limitations by using more complex and multi cell-type models in 3D, as well as efforts to develop readouts and sensors for monitoring tissue- and cell physiology.
MATERIALS TODAY BIO
(2022)
Article
Pharmacology & Pharmacy
Christian Lohasz, Jacqueline Loretan, Dario Sterker, Ekkehard Goerlach, Kasper Renggli, Paul Argast, Olivier Frey, Marion Wiesmann, Markus Wartmann, Martin Rausch, Andreas Hierlemann
Summary: Understanding the pharmacokinetic/pharmacodynamic relationship of a drug candidate is crucial for determining effective treatment regimens. Current testing strategies are inefficient in characterizing in vivo responses to fluctuating drug concentrations during multi-day treatment cycles. The developed microfluidic system enables in vitro culture of three-dimensional spheroids, application of specific dynamic drug exposure profiles, and in-situ analysis of drug effects at tissue and single-cell level.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Engineering, Biomedical
Seunggyu Kim, Joonha Park, Jin-Nyoung Ho, Danhyo Kim, Sangchul Lee, Jessie S. Jeon
Summary: Despite the advantages of microfluidic system, vascular systems for drug transport have been overlooked in microfluidic-based chemotherapeutic screening. In this study, we investigated the chemotherapeutic response of bladder tumor cells using a vascularized tumor on a chip. The chip allowed the establishment of tumor-hydrogel-endothelium interfaces and evaluation of drug resistance and efficacy. Our findings suggest that the vascularized tumor chip enables investigations of chemotherapeutic screening.
Article
Anatomy & Morphology
Amrutha Manigandan, Preethy R. Amruthavarshini, Swaminathan Sethuraman, Anuradha Subramanian
Summary: Modeling the human vascular microphysiological system is crucial for predicting drug response and toxicity accurately. However, the development of an equivalent physiological vascular MPS remains complex due to the challenge of recapitulating the dynamic structural and biological microenvironment similar to native vasculature.
CELLS TISSUES ORGANS
(2022)
Article
Engineering, Biomedical
Jounghyun H. Lee, Kevin L. Shores, Jason J. Breithaupt, Caleb S. Lee, Daniella M. Fodera, Jennifer B. Kwon, Adarsh R. Ettyreddy, Kristin M. Myers, Benny J. Evison, Alexandra K. Suchowerska, Charles A. Gersbach, Kam W. Leong, George A. Truskey
Summary: Atherosclerosis is influenced by PCSK9 activation or repression, and inhibiting PCSK9 can reduce vascular inflammation.
APL BIOENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Marijana Sekulic, Narjes Abdollahi, Lukas Graf, Nikolaus Deigendesch, Raoul Puche, Daniel Bodmer, Vesna Petkovic
Summary: Hearing loss, caused by hair cell damage in the inner ear, is a leading cause of disability worldwide. However, current drug therapies have a low success rate, largely due to differences in inner ear anatomy between species. To address this, researchers have developed a micro-engineered human model of the blood-labyrinth barrier (BLB) on a chip, which mimics the integrity and permeability of human stria vascularis capillaries. This breakthrough represents a major step towards the development of effective treatments for hearing loss.
Review
Pharmacology & Pharmacy
Chengyi Tu, Nathan J. Cunningham, Mao Zhang, Joseph C. Wu
Summary: Evaluation of potential vascular injury is crucial in pharmaceutical development, traditionally relying on animal models, which have shown discrepancies in toxicity compared to human reactions. The emergence of human iPSCs has allowed the creation of human-based vascular models, providing a promising alternative for toxicity testing and a new direction for research. These advancements offer the potential for more clinically relevant and effective safety studies in the field of vascular toxicology.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Analytical
Ann-Katrine Jakobsen, Josephine Geertsen Keller, Maria Gonzalez, Endika Martin-Encinas, Francisco Palacios, Concepcion Alonso, Birgitta Ruth Knudsen, Magnus Stougaard
Summary: DNA sensors can be used for high-throughput drug screening, and in this study, a dual-sensor screening approach was employed to identify three new TDP1 drug candidates that act synergistically with TOP1 poisons, showing clinical potential.
Editorial Material
Cell & Tissue Engineering
Nadia O. Abutaleb, George A. Truskey
Article
Cell & Tissue Engineering
Megan E. Kondash, Anandita Ananthakumar, Alastair Khodabukus, Nenad Bursac, George A. Truskey
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2020)
Article
Cell Biology
Ellen E. Salmon, Jason J. Breithaupt, George A. Truskey
Article
Multidisciplinary Sciences
Anandita Ananthakumar, Yiling Liu, Cristina E. Fernandez, George A. Truskey, Deepak Voora
Review
Cell Biology
Samantha M. Perez, Lindsey T. Brinton, Kimberly A. Kelly
Summary: Plectin, a cytolinker and scaffolding protein, has been identified as a potent driver of malignant hallmarks in various human cancers due to its involvement in key cellular activities contributing to tumorigenesis. Targeting plectin and cancer-specific plectin (CSP) presents an attractive opportunity to directly impede carcinogenesis, with recent evidence highlighting the potential of cell-surface mislocalized proteins as novel therapeutic targets for cancer treatment.
Article
Cell Biology
Samantha M. Perez, Julien Dimastromatteo, Charles N. Landen, Kimberly A. Kelly
Summary: The novel CSP-targeting monoclonal antibody 1H11 demonstrated potent anticancer activity against ovarian cancer by inducing significant and selective cytotoxicity, cell cycle arrest, and inhibiting cell migration. In vivo studies showed tumor growth inhibition, tumor necrosis, and increased sensitivity to chemotherapy.
Review
Engineering, Biomedical
Qiao Zhang, Elia Bosch-Rue, Roman A. Perez, George A. Truskey
Summary: Cardiovascular disease is the leading cause of death among older adults, with a focus on developing TEVS that closely resemble native vessels. Advancements in biofabrication techniques and novel biomaterials are driving this research forward.
APL BIOENGINEERING
(2021)
Article
Engineering, Biomedical
Onur Aydin, Austin P. Passaro, Ritu Raman, Samantha E. Spellicy, Robert P. Weinberg, Roger D. Kamm, Matthew Sample, George A. Truskey, Jeremiah Zartman, Roy D. Dar, Sebastian Palacios, Jason Wang, Jesse Tordoff, Nuria Montserrat, Rashid Bashir, M. Taher A. Saif, Ron Weiss
Summary: Remarkable progress in bioengineering has enabled the formulation of design principles for multicellular engineered living systems (M-CELS), integrating biological parts into functional modules within living machines. These design principles involve genetic circuit manipulation, self-assembly, cell communication, and artificial tissues/organs enabled through various technologies. The review introduces a blueprint for forward production of robust M-CELS and provides practical and theoretical frameworks for their design, control, and optimization. Potential applications range from biopharmaceuticals to environmental bioremediation.
APL BIOENGINEERING
(2022)
Letter
Cardiac & Cardiovascular Systems
Qiao Zhang, Ren-Zhi Zhan, Marisa Patsy, Binjie Li, Yifan Chen, Barbara D. Lipes, Nenad Bursac, George A. Truskey
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Biotechnology & Applied Microbiology
George A. Truskey
Summary: Computational biomechanics, when combined with advanced imaging techniques, can provide detailed patient-specific information for diagnosing and assessing treatments. However, challenges remain in terms of errors and missing information in patient data, computational requirements, and uncertainties in boundary conditions. This review discusses the use of deep learning to address these challenges and integrate large data sets and computational methods for real-time clinical information.
BIOENGINEERING-BASEL
(2023)
Meeting Abstract
Rheumatology
Lauren Covert, George Truskey, Jeffrey Dvergsten
ARTHRITIS & RHEUMATOLOGY
(2022)
Proceedings Paper
Computer Science, Interdisciplinary Applications
Muath Bishawi, Michael Kaplan, Simbarashe Chidyagwai, Jhaymie Cappiello, Anne Cherry, David MacLeod, Ken Gall, Nathan Evans, Michael Kim, Rajib Shaha, John Whittle, Melanie Hollidge, George Truskey, Amanda Randles
Summary: In the early days of the COVID-19 pandemic, we developed a system for efficient and rapid ventilator splitting between patients with varying lung compliances and tidal volume requirements. By using computational modeling and simulation, we identified the optimal splitting method and airflow resistor, providing guidance for medical device design and patient treatment.
COMPUTATIONAL SCIENCE - ICCS 2022, PT III
(2022)
Meeting Abstract
Sport Sciences
Alexander Byron Sklivas, Dante Goss, Nenad Bursac, Alastair Khodahukus, Tim Koves, Deborah Muoio, Lauran Madden, George A. Truskey, William E. Kraus, Monica J. Hubal
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2020)
Article
Multidisciplinary Sciences
Xu Zhang, Muath Bishawi, Ge Zhang, Varun Prasad, Ellen Salmon, Jason J. Breithaupt, Qiao Zhang, George A. Truskey
NATURE COMMUNICATIONS
(2020)
Article
Engineering, Biomedical
Caroline Rhim, William E. Kraus, George A. Truskey
AIMS BIOENGINEERING
(2020)