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This technique enables the study of cell-matrix interactions and is particularly useful for pre-clinical pharmacological studies. More specifically, PCLS are widely used to model the complex pathophysiology of pulmonary fibrosis, an uncurable and progressive interstitial lung disease. Current\n                  <jats:italic>ex vivo<\/jats:italic>\n                  pulmonary fibrosis models expose PCLS to pro-fibrotic biochemical cues over a short timeframe (hours to days) and quickly collect samples for analysis due to viability concerns. This condensed timeline is a limitation to understanding chronic disease mechanisms. To extend the utility of\n                  <jats:italic>ex vivo<\/jats:italic>\n                  pulmonary fibrosis models, PCLS were embedded in engineered hydrogels and exposed to pro-fibrotic biochemical and biophysical cues. Hydrogel-embedded PCLS maintained greater than 80% total cell viability over 3 weeks in culture. Gene expression patterns in samples exposed to pro-fibrotic cues matched trends measured in human fibrotic lung tissue. Finally, treatment with Nintedanib, a Food and Drug Administration approved pulmonary fibrosis drug, moderately reduced fibroblast activation and influenced epithelial cell differentiation. Collectively, these results show that hydrogel-embedded PCLS models of pulmonary fibrosis extend our ability to study fibrotic processes\n                  <jats:italic>ex vivo<\/jats:italic>\n                  and, when applied to human tissues, present a new approach methodology for studying lung disease and treatment.\n                <\/jats:p>","DOI":"10.64898\/2026.03.24.714004","type":"posted-content","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T19:30:45Z","timestamp":1774639845000},"source":"Crossref","is-referenced-by-count":1,"title":["Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation"],"prefix":"10.64898","author":[{"given":"Alicia E.","family":"Tanneberger","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Colorado, Denver | Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Blomberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Colorado, Denver | Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tvishi","family":"Yendamuri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Colorado, Denver | Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"Noelle","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Colorado, Denver | Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G.","family":"Jacot","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Colorado, Denver | Anschutz, Aurora, CO, USA"},{"name":"Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz, Aurora, CO, USA"},{"name":"Department of Pediatrics, University of Colorado, Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janette K.","family":"Burgess","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea M.","family":"Magin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Colorado, Denver | Anschutz, Aurora, CO, USA"},{"name":"Department of Pediatrics, University of Colorado, Anschutz, Aurora, CO, USA"},{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026033107303026000_2026.03.24.714004v1.1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201006-0894CI"},{"key":"2026033107303026000_2026.03.24.714004v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402582"},{"key":"2026033107303026000_2026.03.24.714004v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402584"},{"key":"2026033107303026000_2026.03.24.714004v1.4","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S2213-2600(17)30122-4","article-title":"Clinical trial research in focus: why do so many clinical trials fail in IPF?","volume":"5","year":"2017","journal-title":"Lancet Respir Med"},{"key":"2026033107303026000_2026.03.24.714004v1.5","first-page":"87","article-title":"Challenges of organ shortage for transplantation: solutions and opportunities","volume":"5","year":"2014","journal-title":"Int J Organ Transplant Med"},{"key":"2026033107303026000_2026.03.24.714004v1.6","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00183214"},{"key":"2026033107303026000_2026.03.24.714004v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2013.12.016"},{"key":"2026033107303026000_2026.03.24.714004v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.01.015"},{"key":"2026033107303026000_2026.03.24.714004v1.9","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0442MA"},{"key":"2026033107303026000_2026.03.24.714004v1.10","doi-asserted-by":"crossref","unstructured":"Abo KM , Sainz de Aja J , Lindstrom-Vautrin J , Alysandratos KD , Richards A , Garcia-de-Alba C , Huang J , Hix OT , Werder RB , Bullitt E , Hinds A , Falconer I , Villacorta-Martin C , Jaenisch R , Kim CF , Kotton DN , and Wilson AA . 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