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Existing platforms predominantly model the distal airway, leaving the upper airway, the primary site of respiratory viral entry, insufficiently addressed as an in vitro tissue model for preclinical drug evaluation. We report a six\u2010well, 3D\u2010printed LoC platform fabricated using a photopolymer resin that addresses these limitations. Computational fluid dynamics (CFD)\u2010guided design ensured uniform perfusion across all six wells, enabling parallel tissue culture within a single device. The photopolymer architecture eliminated mechanical deformation of the device microchannels under prolonged perfusion and demonstrated significantly reduced small\u2010molecule adsorption relative to PDMS, improving quantitative reliability for drug evaluation workflows. Human tracheobronchial epithelial cells differentiated at air\u2010liquid interface expressed MUC5AC and cytokeratin\u201014, formed continuous ZO\u20101 tight junctions, and achieved a transepithelial electrical resistance of ~800\u2009\u03a9\u00b7cm\n                    <jats:sup>2<\/jats:sup>\n                    , consistent with physiological barrier integrity. A GelMA\u2010based stromal compartment, fabricated by extrusion bioprinting of lung fibroblast\u2010 and THP\u20101 monocyte\u2010laden bioink, established a layered epithelial\u2010stromal\u2010immune architecture. Functional validation demonstrated IL\u20106 and IL\u20108 elevation following SARS\u2010CoV\u20102 spike S1 stimulation, IFN\u2010\u03b3\u2010driven modulation of apical ACE2 expression, and coordinated TNF\u2010\u03b1, IL\u20106, and IL\u20108 release during Influenza A infection, all suppressed by oseltamivir treatment. This platform integrates CFD\u2010optimized multi\u2010well device fabrication, extrusion bioprinting of stromal constructs, and photopolymer resin\u2010based microfluidic manufacturing into a reproducible, human\u2010relevant upper airway model for respiratory infection research and preclinical antiviral drug evaluation.\n                  <\/jats:p>","DOI":"10.1002\/btpr.88538","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:41:56Z","timestamp":1783996916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 3D\u2010printed multi\u2010well lung\u2010on\u2010chip platform with bioprinted stromal compartment for upper airway tissue culture and antiviral drug evaluation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-8989","authenticated-orcid":false,"given":"Pooja","family":"Sawant","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Institute of Chemical Technology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudepalya Renukaiah","family":"Rudramurthy","sequence":"additional","affiliation":[{"name":"Department of Virology Foundation for Neglected Disease Research  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Kailaje","sequence":"additional","affiliation":[{"name":"Department of Virology Foundation for Neglected Disease Research  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-1340","authenticated-orcid":false,"given":"Radha Krishan","family":"Shandil","sequence":"additional","affiliation":[{"name":"Department of Virology Foundation for Neglected Disease Research  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-7399","authenticated-orcid":false,"given":"Shridhar","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Virology Foundation for Neglected Disease Research  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratnesh","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Biotechnology Institute of Chemical Technology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajakta","family":"Dandekar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Institute of Chemical Technology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1188302"},{"key":"e_1_2_11_3_1","unstructured":"Emulate's Lung\u2010Chip Demonstrates New Capabilities to Predict Human Lung Inflammation and Drug Responses in Asthma and COPD | Emulate.https:\/\/emulatebio.com\/press\/lung-chip-new-capabilities\/. 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