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This study develops a self\u2010folding gelatin\u2010based bilayer scaffold for trachea engineering exploiting the 4D bioprinting approach. Starting from a 2D flat configuration, upon hydration, the scaffold automatically forms a closed tubular structure. An analytical model, based on Timoshenko's beam thermostats, is developed and validated to predict the radius of curvature of the scaffold. The 4D bioprinted structure is tested with airway fibroblast, lung endothelial cells, and cartilage progenitor cells (CPCs) toward the development of a tissue\u2010engineered trachea. Cells are seeded on the scaffold in its initial flat configuration, maintain their position after the scaffold actuation, and proliferate over or inside it. The ability of CPCs to differentiate toward mature cartilage is evaluated. Interestingly, real\u2010time PCR reveals that differentiating CPCs on the 4D bioprinted scaffold promotes healthier cartilage formation, if compared with CPCs cultured on 2D static flat scaffold. Thus, CPCs can perceive scaffold folding and its final curvature and react to it, toward the formation of mature cartilage for the airway.<\/jats:p>","DOI":"10.1002\/admt.202401210","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T09:09:58Z","timestamp":1735204198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["4D Bioprinted Self\u2010Folding Scaffolds Enhance Cartilage Formation in the Engineering of Trachea"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-4990","authenticated-orcid":false,"given":"Irene","family":"Chiesa","sequence":"first","affiliation":[{"name":"Research Center \u201cE. 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