{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T18:16:32Z","timestamp":1771956992846,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,18]]},"group-title":"Bioengineering","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK127436"],"award-info":[{"award-number":["R01DK127436"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Pancreatic ductal organoids (PDOs) generated from human induced pluripotent stem cells (iPSCs) can be used to model pancreatic diseases and to conduct drug screening\/testing. However, current protocols for generating PDOs rely heavily on tumor-derived Matrigel, which has been shown to upregulate oncogenes. Furthermore, Matrigel has undefined composition and weak mechanical properties that hamper mechanistic studies of cell-material interactions. In this study, we explore photo-clickable decellularized small intestine submucosa-norbornene (dSIS-NB) hydrogels as a Matrigel replacement for generating human iPSC-derived PDOs. To achieve this, pancreatic progenitors (PP) were first differentiated in conventional two-dimensional (2D) culture, aggregated into spheroids, then encapsulated and differentiated within dSIS-NB hydrogels with tunable stiffness. The differentiated organoids were analyzed by morphology, expression of key pancreatic ductal markers, and single-cell RNA sequencing (scRNA-seq). Post-differentiation, PDOs generated in stiffer photo-clickable dSIS-NB hydrogels (shear moduli \u223c2.5 kPa) maintained ductal epithelial phenotype and exhibited pronounced forskolin-induced swelling. In contrast, differentiation of PP spheroids in softer dSIS-NB gels (shear moduli \u223c0.9 kPa) and Matrigel resulted in a persistent mesenchymal phenotype and failed to generate functional PDOs. Finally, scRNA-seq results revealed that stiffer dSIS-NB hydrogels strongly biased ductal cell differentiation, yielding greater than 97% ductal progeny.<\/jats:p>","DOI":"10.64898\/2026.02.16.706185","type":"posted-content","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T16:10:22Z","timestamp":1771431022000},"source":"Crossref","is-referenced-by-count":0,"title":["Photo-click Decellularized Matrix Hydrogels for Generating Pancreatic Ductal Organoids"],"prefix":"10.64898","author":[{"given":"Ngoc Ha","family":"Luong","sequence":"first","affiliation":[{"name":"Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN. 47907, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunming","family":"Shao","sequence":"additional","affiliation":[{"name":"Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN. 47907, USA"},{"name":"Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, 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