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Here, stem cell technology is combined with 4D bioprinting, a fabrication process that utilizes additive manufacturing, to generate a 4D\u2010neural tube (4D\u2010NT). This consists of a scaffold that can self\u2010fold over time, which is then populated with iPSC\u2010derived neuroprogenitors, mimicking neural tube cellular architecture. The scaffold's \u201csmart\u201d self\u2010folding behavior is driven by the differential swelling properties of bilayer films, which create a deformation gradient upon hydration. Cellular analyses reveal a highly efficient induction of neuroprogenitors on 4D\u2010NTs, demonstrating the ability of this model to mimic the spatial and structural complexity of the developing human neural tube. Furthermore, 4D\u2010NTs seeded with iPSCs with a mutation in\n                    <jats:italic>WDR62<\/jats:italic>\n                    , associated with autosomal recessive primary microcephaly (MCPH), recapitulate the earlier observations obtained in 2D\/3D neural cultures, thereby validating the newly developed 4D\u2010NT platform and suggesting it represents a tool that can facilitate understanding of human neural development and disease.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202501405","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:37:03Z","timestamp":1761205023000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Human Neural Tube Model Using 4D Self\u2010Folding Smart Scaffolds"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-3423","authenticated-orcid":false,"given":"Claudia","family":"Dell'Amico","sequence":"first","affiliation":[{"name":"University of Pisa Department of Biology, Unit of Cell, Molecular, and Developmental Biology  Pisa 56127 Italy"},{"name":"University of Pisa Department of Clinical and Experimental Medicine  Pisa 56126 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Chiesa","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Information Engineering and Research Center Enrico Piaggio  Pisa 56122 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Toffano","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Biology, Unit of Cell, Molecular, and Developmental Biology  Pisa 56127 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Esposito","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Information Engineering and Research Center Enrico Piaggio  Pisa 56122 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piera","family":"Mancini","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Information Engineering and Research Center Enrico Piaggio  Pisa 56122 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Magliaro","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Information Engineering and Research Center Enrico Piaggio  Pisa 56122 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Louvi","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and of Neuroscience Yale School of Medicine  New Haven Connecticut 06520\u20108082 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-3571","authenticated-orcid":false,"given":"Carmelo","family":"De Maria","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Information Engineering and Research Center Enrico Piaggio  Pisa 56122 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8517-930X","authenticated-orcid":false,"given":"Marco","family":"Onorati","sequence":"additional","affiliation":[{"name":"University of Pisa Department of Biology, Unit of Cell, Molecular, and Developmental Biology  Pisa 56127 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470514559.ch5"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.145904"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01121-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/embr.201438447"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081893"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2643"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81537-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20333"},{"key":"e_1_2_9_10_1","volume":"56","author":"Gray J.","year":"2011","journal-title":"J. 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