{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:38:46Z","timestamp":1768509526412,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,8]]},"group-title":"Bioengineering","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Trachea defects that required surgical interventions are increasing in number in the recent years, especially for pediatric patients. However, current gold standards, such as biological grafts and synthetic prothesis, do not represent an effective solution, due to the lack of mimicry and regeneration capability. Bioprinting is a cutting-edge approach for the fabrication of biomimetic scaffold to empower tissue engineering toward trachea replacement. In this study, we developed a self-folding gelatin-based bilayer scaffold for trachea engineering, exploiting the 4D bioprinting approach, namely the fabrication of dynamic scaffolds, able to shape morph in a predefined way after the application of an environmental stimulus. Indeed, starting form a 2D flat position, upon hydration, this scaffold forms a closed tubular structure. An analytical model, based on Timoshenko\u2019s beam thermostats, was developed, and validated to predict the radius of curvature of the scaffold according to the material properties and the scaffold geometry. The 4D bioprinted structure was tested with airway fibroblast, lung endothelial cells and ear chondral progenitor cells (eCPCs) toward the development of a tissue engineered trachea. Cells were seeded on the scaffold in its initial flat position, maintained their position after the scaffold actuation and proliferated over or inside it. The ability of eCPCs to differentiate towards mature cartialge was evaluated. Interestingly, real-time PCR revealed that differentiating eCPCs on the 4D bioprinted scaffold promote healthy cartilage formation, if compared with eCPCs cultured on 2D static scaffold. Thus, eCPCs can perceive scaffold folding and its final curvature and to react to it, towards the formation of mature cartilage for the airway.<\/jats:p>","DOI":"10.1101\/2023.12.06.570378","type":"posted-content","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T14:35:11Z","timestamp":1702046111000},"source":"Crossref","is-referenced-by-count":0,"title":["4D bioprinted self-folding scaffolds enhance cartilage formation in the engineering of trachea"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-4990","authenticated-orcid":false,"given":"Irene","family":"Chiesa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2986-7251","authenticated-orcid":false,"given":"Alessio","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9414-9994","authenticated-orcid":false,"given":"Giovanni","family":"Vozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-5531","authenticated-orcid":false,"given":"Riccardo","family":"Gottardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-3571","authenticated-orcid":false,"given":"Carmelo","family":"De Maria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"June","key":"2023121114250747000_2023.12.06.570378v1.1","first-page":"1","article-title":"Three - dimensional and four - dimensional printing in otolaryngology","volume":"48","year":"2023","journal-title":"MRS Bulletin"},{"issue":"March","key":"2023121114250747000_2023.12.06.570378v1.2","first-page":"112005","article-title":"Recent advances in bioprinting technologies for engineering different cartilage-based tissues","volume":"123","year":"2021","journal-title":"Materials Science and Engineering C"},{"issue":"February","key":"2023121114250747000_2023.12.06.570378v1.3","first-page":"219","article-title":"Surgical management of children presenting with surgical-needed tracheal stenosis","volume":"108","year":"2018","journal-title":"International Journal of Pediatric Otorhinolaryngology"},{"key":"2023121114250747000_2023.12.06.570378v1.4","doi-asserted-by":"publisher","DOI":"10.3390\/life11040348"},{"issue":"2","key":"2023121114250747000_2023.12.06.570378v1.5","first-page":"1","article-title":"Reconstruction of defects of the trachea","volume":"28","year":"2017","journal-title":"Journal of Materials Science: Materials in Medicine"},{"key":"2023121114250747000_2023.12.06.570378v1.6","doi-asserted-by":"publisher","DOI":"10.1001\/archoto.2011.85"},{"issue":"5","key":"2023121114250747000_2023.12.06.570378v1.7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0022-5223(19)33356-2","article-title":"Replacement of Tracheobronchial Defects With Autogenous Pericardium","volume":"48","year":"1964","journal-title":"The Journal of thoracic and cardiovascular surgery"},{"key":"2023121114250747000_2023.12.06.570378v1.8","doi-asserted-by":"crossref","unstructured":"J. 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