A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.
Identifieur interne : 000057 ( Main/Corpus ); précédent : 000056; suivant : 000058A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.
Auteurs : Longlong Si ; Haiqing Bai ; Melissa Rodas ; Wuji Cao ; Crystal Yuri Oh ; Amanda Jiang ; Rasmus Moller ; Daisy Hoagland ; Kohei Oishi ; Shu Horiuchi ; Skyler Uhl ; Daniel Blanco-Melo ; Randy A. Albrecht ; Wen-Chun Liu ; Tristan Jordan ; Benjamin E. Nilsson-Payant ; Ilona Golynker ; Justin Frere ; James Logue ; Robert Haupt ; Marisa Mcgrath ; Stuart Weston ; Tian Zhang ; Roberto Plebani ; Mercy Soong ; Atiq Nurani ; Seong Min Kim ; Danni Y. Zhu ; Kambez H. Benam ; Girija Goyal ; Sarah E. Gilpin ; Rachelle Prantil-Baun ; Steven P. Gygi ; Rani K. Powers ; Kenneth E. Carlson ; Matthew Frieman ; Benjamin R. Tenoever ; Donald E. IngberSource :
- Nature biomedical engineering [ 2157-846X ] ; 2021.
Abstract
The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.
DOI: 10.1038/s41551-021-00718-9
PubMed: 33941899
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pubmed:33941899Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.</title>
<author><name sortKey="Si, Longlong" sort="Si, Longlong" uniqKey="Si L" first="Longlong" last="Si">Longlong Si</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bai, Haiqing" sort="Bai, Haiqing" uniqKey="Bai H" first="Haiqing" last="Bai">Haiqing Bai</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rodas, Melissa" sort="Rodas, Melissa" uniqKey="Rodas M" first="Melissa" last="Rodas">Melissa Rodas</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cao, Wuji" sort="Cao, Wuji" uniqKey="Cao W" first="Wuji" last="Cao">Wuji Cao</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Oh, Crystal Yuri" sort="Oh, Crystal Yuri" uniqKey="Oh C" first="Crystal Yuri" last="Oh">Crystal Yuri Oh</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jiang, Amanda" sort="Jiang, Amanda" uniqKey="Jiang A" first="Amanda" last="Jiang">Amanda Jiang</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Moller, Rasmus" sort="Moller, Rasmus" uniqKey="Moller R" first="Rasmus" last="Moller">Rasmus Moller</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hoagland, Daisy" sort="Hoagland, Daisy" uniqKey="Hoagland D" first="Daisy" last="Hoagland">Daisy Hoagland</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Oishi, Kohei" sort="Oishi, Kohei" uniqKey="Oishi K" first="Kohei" last="Oishi">Kohei Oishi</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Horiuchi, Shu" sort="Horiuchi, Shu" uniqKey="Horiuchi S" first="Shu" last="Horiuchi">Shu Horiuchi</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Uhl, Skyler" sort="Uhl, Skyler" uniqKey="Uhl S" first="Skyler" last="Uhl">Skyler Uhl</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Blanco Melo, Daniel" sort="Blanco Melo, Daniel" uniqKey="Blanco Melo D" first="Daniel" last="Blanco-Melo">Daniel Blanco-Melo</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Albrecht, Randy A" sort="Albrecht, Randy A" uniqKey="Albrecht R" first="Randy A" last="Albrecht">Randy A. Albrecht</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Liu, Wen Chun" sort="Liu, Wen Chun" uniqKey="Liu W" first="Wen-Chun" last="Liu">Wen-Chun Liu</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jordan, Tristan" sort="Jordan, Tristan" uniqKey="Jordan T" first="Tristan" last="Jordan">Tristan Jordan</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nilsson Payant, Benjamin E" sort="Nilsson Payant, Benjamin E" uniqKey="Nilsson Payant B" first="Benjamin E" last="Nilsson-Payant">Benjamin E. Nilsson-Payant</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Golynker, Ilona" sort="Golynker, Ilona" uniqKey="Golynker I" first="Ilona" last="Golynker">Ilona Golynker</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Frere, Justin" sort="Frere, Justin" uniqKey="Frere J" first="Justin" last="Frere">Justin Frere</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Logue, James" sort="Logue, James" uniqKey="Logue J" first="James" last="Logue">James Logue</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Haupt, Robert" sort="Haupt, Robert" uniqKey="Haupt R" first="Robert" last="Haupt">Robert Haupt</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mcgrath, Marisa" sort="Mcgrath, Marisa" uniqKey="Mcgrath M" first="Marisa" last="Mcgrath">Marisa Mcgrath</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weston, Stuart" sort="Weston, Stuart" uniqKey="Weston S" first="Stuart" last="Weston">Stuart Weston</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, Tian" sort="Zhang, Tian" uniqKey="Zhang T" first="Tian" last="Zhang">Tian Zhang</name>
<affiliation><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Plebani, Roberto" sort="Plebani, Roberto" uniqKey="Plebani R" first="Roberto" last="Plebani">Roberto Plebani</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Soong, Mercy" sort="Soong, Mercy" uniqKey="Soong M" first="Mercy" last="Soong">Mercy Soong</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nurani, Atiq" sort="Nurani, Atiq" uniqKey="Nurani A" first="Atiq" last="Nurani">Atiq Nurani</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kim, Seong Min" sort="Kim, Seong Min" uniqKey="Kim S" first="Seong Min" last="Kim">Seong Min Kim</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhu, Danni Y" sort="Zhu, Danni Y" uniqKey="Zhu D" first="Danni Y" last="Zhu">Danni Y. Zhu</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Benam, Kambez H" sort="Benam, Kambez H" uniqKey="Benam K" first="Kambez H" last="Benam">Kambez H. Benam</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Goyal, Girija" sort="Goyal, Girija" uniqKey="Goyal G" first="Girija" last="Goyal">Girija Goyal</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gilpin, Sarah E" sort="Gilpin, Sarah E" uniqKey="Gilpin S" first="Sarah E" last="Gilpin">Sarah E. Gilpin</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Prantil Baun, Rachelle" sort="Prantil Baun, Rachelle" uniqKey="Prantil Baun R" first="Rachelle" last="Prantil-Baun">Rachelle Prantil-Baun</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gygi, Steven P" sort="Gygi, Steven P" uniqKey="Gygi S" first="Steven P" last="Gygi">Steven P. Gygi</name>
<affiliation><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Powers, Rani K" sort="Powers, Rani K" uniqKey="Powers R" first="Rani K" last="Powers">Rani K. Powers</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Carlson, Kenneth E" sort="Carlson, Kenneth E" uniqKey="Carlson K" first="Kenneth E" last="Carlson">Kenneth E. Carlson</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tenoever, Benjamin R" sort="Tenoever, Benjamin R" uniqKey="Tenoever B" first="Benjamin R" last="Tenoever">Benjamin R. Tenoever</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ingber, Donald E" sort="Ingber, Donald E" uniqKey="Ingber D" first="Donald E" last="Ingber">Donald E. Ingber</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.</title>
<author><name sortKey="Si, Longlong" sort="Si, Longlong" uniqKey="Si L" first="Longlong" last="Si">Longlong Si</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bai, Haiqing" sort="Bai, Haiqing" uniqKey="Bai H" first="Haiqing" last="Bai">Haiqing Bai</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rodas, Melissa" sort="Rodas, Melissa" uniqKey="Rodas M" first="Melissa" last="Rodas">Melissa Rodas</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cao, Wuji" sort="Cao, Wuji" uniqKey="Cao W" first="Wuji" last="Cao">Wuji Cao</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Oh, Crystal Yuri" sort="Oh, Crystal Yuri" uniqKey="Oh C" first="Crystal Yuri" last="Oh">Crystal Yuri Oh</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jiang, Amanda" sort="Jiang, Amanda" uniqKey="Jiang A" first="Amanda" last="Jiang">Amanda Jiang</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Moller, Rasmus" sort="Moller, Rasmus" uniqKey="Moller R" first="Rasmus" last="Moller">Rasmus Moller</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hoagland, Daisy" sort="Hoagland, Daisy" uniqKey="Hoagland D" first="Daisy" last="Hoagland">Daisy Hoagland</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Oishi, Kohei" sort="Oishi, Kohei" uniqKey="Oishi K" first="Kohei" last="Oishi">Kohei Oishi</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Horiuchi, Shu" sort="Horiuchi, Shu" uniqKey="Horiuchi S" first="Shu" last="Horiuchi">Shu Horiuchi</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Uhl, Skyler" sort="Uhl, Skyler" uniqKey="Uhl S" first="Skyler" last="Uhl">Skyler Uhl</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Blanco Melo, Daniel" sort="Blanco Melo, Daniel" uniqKey="Blanco Melo D" first="Daniel" last="Blanco-Melo">Daniel Blanco-Melo</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Albrecht, Randy A" sort="Albrecht, Randy A" uniqKey="Albrecht R" first="Randy A" last="Albrecht">Randy A. Albrecht</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Liu, Wen Chun" sort="Liu, Wen Chun" uniqKey="Liu W" first="Wen-Chun" last="Liu">Wen-Chun Liu</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jordan, Tristan" sort="Jordan, Tristan" uniqKey="Jordan T" first="Tristan" last="Jordan">Tristan Jordan</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nilsson Payant, Benjamin E" sort="Nilsson Payant, Benjamin E" uniqKey="Nilsson Payant B" first="Benjamin E" last="Nilsson-Payant">Benjamin E. Nilsson-Payant</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Golynker, Ilona" sort="Golynker, Ilona" uniqKey="Golynker I" first="Ilona" last="Golynker">Ilona Golynker</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Frere, Justin" sort="Frere, Justin" uniqKey="Frere J" first="Justin" last="Frere">Justin Frere</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Logue, James" sort="Logue, James" uniqKey="Logue J" first="James" last="Logue">James Logue</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Haupt, Robert" sort="Haupt, Robert" uniqKey="Haupt R" first="Robert" last="Haupt">Robert Haupt</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mcgrath, Marisa" sort="Mcgrath, Marisa" uniqKey="Mcgrath M" first="Marisa" last="Mcgrath">Marisa Mcgrath</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weston, Stuart" sort="Weston, Stuart" uniqKey="Weston S" first="Stuart" last="Weston">Stuart Weston</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, Tian" sort="Zhang, Tian" uniqKey="Zhang T" first="Tian" last="Zhang">Tian Zhang</name>
<affiliation><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Plebani, Roberto" sort="Plebani, Roberto" uniqKey="Plebani R" first="Roberto" last="Plebani">Roberto Plebani</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Soong, Mercy" sort="Soong, Mercy" uniqKey="Soong M" first="Mercy" last="Soong">Mercy Soong</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nurani, Atiq" sort="Nurani, Atiq" uniqKey="Nurani A" first="Atiq" last="Nurani">Atiq Nurani</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kim, Seong Min" sort="Kim, Seong Min" uniqKey="Kim S" first="Seong Min" last="Kim">Seong Min Kim</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhu, Danni Y" sort="Zhu, Danni Y" uniqKey="Zhu D" first="Danni Y" last="Zhu">Danni Y. Zhu</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Benam, Kambez H" sort="Benam, Kambez H" uniqKey="Benam K" first="Kambez H" last="Benam">Kambez H. Benam</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Goyal, Girija" sort="Goyal, Girija" uniqKey="Goyal G" first="Girija" last="Goyal">Girija Goyal</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gilpin, Sarah E" sort="Gilpin, Sarah E" uniqKey="Gilpin S" first="Sarah E" last="Gilpin">Sarah E. Gilpin</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Prantil Baun, Rachelle" sort="Prantil Baun, Rachelle" uniqKey="Prantil Baun R" first="Rachelle" last="Prantil-Baun">Rachelle Prantil-Baun</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gygi, Steven P" sort="Gygi, Steven P" uniqKey="Gygi S" first="Steven P" last="Gygi">Steven P. Gygi</name>
<affiliation><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Powers, Rani K" sort="Powers, Rani K" uniqKey="Powers R" first="Rani K" last="Powers">Rani K. Powers</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Carlson, Kenneth E" sort="Carlson, Kenneth E" uniqKey="Carlson K" first="Kenneth E" last="Carlson">Kenneth E. Carlson</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name>
<affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tenoever, Benjamin R" sort="Tenoever, Benjamin R" uniqKey="Tenoever B" first="Benjamin R" last="Tenoever">Benjamin R. Tenoever</name>
<affiliation><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ingber, Donald E" sort="Ingber, Donald E" uniqKey="Ingber D" first="Donald E" last="Ingber">Donald E. Ingber</name>
<affiliation><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature biomedical engineering</title>
<idno type="eISSN">2157-846X</idno>
<imprint><date when="2021" type="published">2021</date>
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<front><div type="abstract" xml:lang="en">The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33941899</PMID>
<DateRevised><Year>2021</Year>
<Month>05</Month>
<Day>04</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2157-846X</ISSN>
<JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year>
<Month>May</Month>
<Day>03</Day>
</PubDate>
</JournalIssue>
<Title>Nature biomedical engineering</Title>
<ISOAbbreviation>Nat Biomed Eng</ISOAbbreviation>
</Journal>
<ArticleTitle>A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.</ArticleTitle>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41551-021-00718-9</ELocationID>
<Abstract><AbstractText>The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Si</LastName>
<ForeName>Longlong</ForeName>
<Initials>L</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-0504-1659</Identifier>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Bai</LastName>
<ForeName>Haiqing</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rodas</LastName>
<ForeName>Melissa</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cao</LastName>
<ForeName>Wuji</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oh</LastName>
<ForeName>Crystal Yuri</ForeName>
<Initials>CY</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jiang</LastName>
<ForeName>Amanda</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Moller</LastName>
<ForeName>Rasmus</ForeName>
<Initials>R</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-8452-0761</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hoagland</LastName>
<ForeName>Daisy</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oishi</LastName>
<ForeName>Kohei</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Horiuchi</LastName>
<ForeName>Shu</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Uhl</LastName>
<ForeName>Skyler</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Blanco-Melo</LastName>
<ForeName>Daniel</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Albrecht</LastName>
<ForeName>Randy A</ForeName>
<Initials>RA</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-4008-503X</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Wen-Chun</ForeName>
<Initials>WC</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jordan</LastName>
<ForeName>Tristan</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nilsson-Payant</LastName>
<ForeName>Benjamin E</ForeName>
<Initials>BE</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-2661-7837</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Golynker</LastName>
<ForeName>Ilona</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Frere</LastName>
<ForeName>Justin</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-7514-8873</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Logue</LastName>
<ForeName>James</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-7410-9741</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Haupt</LastName>
<ForeName>Robert</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McGrath</LastName>
<ForeName>Marisa</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-7451-4958</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Weston</LastName>
<ForeName>Stuart</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Tian</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Plebani</LastName>
<ForeName>Roberto</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Soong</LastName>
<ForeName>Mercy</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nurani</LastName>
<ForeName>Atiq</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Seong Min</ForeName>
<Initials>SM</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhu</LastName>
<ForeName>Danni Y</ForeName>
<Initials>DY</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Benam</LastName>
<ForeName>Kambez H</ForeName>
<Initials>KH</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Goyal</LastName>
<ForeName>Girija</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gilpin</LastName>
<ForeName>Sarah E</ForeName>
<Initials>SE</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Prantil-Baun</LastName>
<ForeName>Rachelle</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gygi</LastName>
<ForeName>Steven P</ForeName>
<Initials>SP</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0001-7626-0034</Identifier>
<AffiliationInfo><Affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Powers</LastName>
<ForeName>Rani K</ForeName>
<Initials>RK</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Carlson</LastName>
<ForeName>Kenneth E</ForeName>
<Initials>KE</Initials>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Frieman</LastName>
<ForeName>Matthew</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-0107-0775</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>tenOever</LastName>
<ForeName>Benjamin R</ForeName>
<Initials>BR</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-0324-3078</Identifier>
<AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ingber</LastName>
<ForeName>Donald E</ForeName>
<Initials>DE</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-4319-6520</Identifier>
<AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2021</Year>
<Month>05</Month>
<Day>03</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Nat Biomed Eng</MedlineTA>
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<ISSNLinking>2157-846X</ISSNLinking>
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<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>12</Month>
<Day>31</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2021</Year>
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<Day>19</Day>
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<ArticleId IdType="doi">10.1038/s41551-021-00718-9</ArticleId>
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