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However, graft failure resulting from necrosis and insufficient integration with native tissue due to lack of oxygen and nutrient transportation remains a concern. To overcome these drawbacks, this study aims to develop a 3D printed polycaprolactone layered construct with a LEGO<jats:sup>\u00ae<\/jats:sup>-inspired interlocking mechanism enabling spatial distribution of biological components. To highlight its <jats:italic>in vitro<\/jats:italic> osteogenic potential, human mesenchymal stromal cells are cultured onto Bio-Gide<jats:sup>\u00ae<\/jats:sup> Compressed collagen (Col) membranes, which are embedded within the layered construct for 28 d. The osteogenic response is assessed through the measurement of proliferation, relevant markers for osteogenesis including alkaline phosphatase (ALP) activity, expression of transcriptional genes (SP7, RUNX2\/SOX9) as well matrix-related genes (COL1A1, ALPL IBSP, SPP1), osteoprotegerin secretion. <jats:italic>In vitro<\/jats:italic> osteogenic differentiation results showed increased levels of these osteogenic markers, indicating the layered construct\u2019s potential to support osteogenesis. In this study, a novel workflow of 3D printing a patient-specific LEGO<jats:sup>\u00ae<\/jats:sup>-inspired layered construct that can spatially deliver biological elements was successfully demonstrated. These layered constructs have the potential to be employed as a bone tissue engineering strategy, with particular focus on the repair of large mandibular defects.<\/jats:p>","DOI":"10.1088\/1758-5090\/ad6931","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T22:52:37Z","timestamp":1722379957000},"page":"045020","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["In vitro osteogenesis of hMSCs on collagen membranes embedded within LEGO<sup>\u00ae<\/sup>-inspired 3D printed PCL constructs for mandibular bone repair"],"prefix":"10.1088","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-4353","authenticated-orcid":false,"given":"Daphne","family":"van der Heide","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luan Phelipe","family":"Hatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E","family":"Pirera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela R","family":"Armiento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-1517","authenticated-orcid":true,"given":"Martin J","family":"Stoddart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"bfad6931bib1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1758-3284-3-23","article-title":"Reconstruction of mandibular defects\u2014clinical retrospective research over a 10-year period","volume":"3","author":"Rana","year":"2011","journal-title":"Head Neck Oncol."},{"key":"bfad6931bib2","doi-asserted-by":"publisher","DOI":"10.1016\/j.adoms.2021.100229","article-title":"Reconstruction of large mandibular bone defects extended to the condyle using patient-specific implants based on CAD-CAM technology and 3D printing","volume":"5","author":"Ismail","year":"2022","journal-title":"Adv. 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