{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:38Z","timestamp":1785427298191,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Children\u2019s Health Foundation","award":["RPAC-2013-06"],"award-info":[{"award-number":["RPAC-2013-06"]}]},{"name":"The Children\u2019s Health Foundation","award":["RPAC-19-01"],"award-info":[{"award-number":["RPAC-19-01"]}]},{"name":"Research Ireland Pathway Award","award":["21\/Path-S\/9306"],"award-info":[{"award-number":["21\/Path-S\/9306"]}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"crossref","award":["EIA-2022-009"],"award-info":[{"award-number":["EIA-2022-009"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"crossref"}]},{"award":["EIA-2022-009"],"award-info":[{"award-number":["EIA-2022-009"]}],"id":[{"id":"https:\/\/ror.org\/003hb2249","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Craniosynostosis is a congenital bone developmental condition characterized by the premature ossification of calvarial sutures, leading to restricted skull expansion and potential neurological complications. Although little is known about the signaling that governs this accelerated fusion, our research group has previously identified a stiffness-dependent upregulation of osteogenic genes in cells derived from fused sutures, highlighting the role of mechanotransduction in disease progression. Building on these findings, the present study describes the development of a unique patient-derived three-dimensional (3D) tissue-engineering (TE) model of non-syndromic craniosynostosis (NS-CS) to investigate how extracellular matrix (ECM) composition and biochemical cues regulate ossification timing and patterns. Cells isolated from clinically relevant tissues, surgically obtained from patent and prematurely fused calvarial sutures of pediatric NS-CS patients, were characterized and cultured under both two-dimensional (2D) and 3D suture-mimicking conditions. Comparative analysis revealed differences in cellular responsiveness between cells isolated from fused and patent sutures across the different experimental conditions, with cells from fused sutures consistently exhibiting higher expression of osteogenic markers. Notably, the elevated expression of osteogenic and chondrogenic markers suggested the possible involvement of endochondral-like ossification mechanisms during the pathological process of suture fusion. This patient-derived model was designed to recapitulate biophysical and biochemical features of the extracellular matrix of healthy and pathological sutures, serving as a tool for future research, helping us to understand the underlying mechanisms behind the pathophysiology of craniosynostosis.<\/jats:p>","DOI":"10.3390\/bioengineering13070746","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:58:04Z","timestamp":1782799084000},"page":"746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 3D Tissue-Engineering Model of Craniosynostosis to Study the Microenvironmental Signals Leading to Premature Suture Ossification"],"prefix":"10.3390","volume":"13","author":[{"given":"Mariangela","family":"Meyer","sequence":"first","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin (TCD), D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holmfridur","family":"Rist Jonsdottir","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin (TCD), D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Amado","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health 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Children\u2019s Health Ireland (CHI) at Temple Street, D01 YC67 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-0542","authenticated-orcid":false,"given":"Kulwinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"School of Pharmacy & Biomolecular Sciences (PBS), Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Hodgkinson","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin (TCD), D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan J.","family":"Murray","sequence":"additional","affiliation":[{"name":"National Paediatric Craniofacial Centre, Children\u2019s Health Ireland (CHI) at Temple Street, D01 YC67 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-5590","authenticated-orcid":false,"given":"Arlyng","family":"Gonz\u00e1lez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin (TCD), D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-8005","authenticated-orcid":false,"given":"Fergal J.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin (TCD), D02 PN40 Dublin, Ireland"},{"name":"Trinity Centre for Bioengineering, Trinity College Dublin (TCD), D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1053\/j.sodo.2005.07.004","article-title":"Genetic Factors Influencing Morphogenesis and Growth of Sutures and Synchondroses 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