{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:35:01Z","timestamp":1785429301789,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-DE027662"],"award-info":[{"award-number":["R01-DE027662"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 AR069620"],"award-info":[{"award-number":["P30 AR069620"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01-DE027662"],"award-info":[{"award-number":["R01-DE027662"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 AR069620"],"award-info":[{"award-number":["P30 AR069620"]}],"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Michigan Dental School Le Gro"},{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Craniosynostosis is the premature fusion of skull bones due to loss of stem\/progenitor cells located in non-mineralized tissue between growing cranial bones of infants. We generated scaffolds from a biodegradable biomaterial with small interconnected pores (125\u2013250 \u03bcm diameter), previously shown to maintain stemness of a mesenchymal cell population, to further develop a method for the creation of an artificial cranial bone stem cell niche. Polymer scaffolds of consistent pore size were fabricated using a molecular-sieved sugar sphere casting technique with poly-l-lactic acid. A rectangular surgical defect within the parietal bone of juvenile mice was created. The three groups included sham animals with surgery but no scaffold, experimental animals with surgery plus an implanted cell-free scaffold, and experimental animals with surgery plus an implanted bone mesenchymal cell-seeded scaffold. Healing at the surgical site was evaluated at 4 and 12 weeks after surgery by micro-CT and histology. Surgical site bone volume fraction and bone mineral density were significantly greater at twelve than four weeks in the sham group but not in either of the scaffold groups. At twelve weeks, the surgical site bone volume fraction and bone mineral density were significantly lower in the cell-seeded scaffold as compared to the sham animal group. At twelve weeks, the anterior and middle cranial vault widths were significantly greater in the cell-seeded scaffold as compared to the sham animal group on the surgery side of the skulls. Less mineralization was evident within the cell-seeded than the cell-free scaffolds by histology. Based on these findings, scaffolds of sufficiently small pore size seeded with autologous bone mesenchymal stem cells could function as an artificial cranial stem cell niche to inhibit surgical-site mineralization and promote cranial growth.<\/jats:p>","DOI":"10.3390\/bioengineering13040420","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:09:54Z","timestamp":1775138994000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Initial In Vivo Analyses of Small Pore Polymer Scaffolds for Creation of an Artificial Cranial Stem Cell Niche"],"prefix":"10.3390","volume":"13","author":[{"given":"Elizabeth","family":"Soulas","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8074-7117","authenticated-orcid":false,"given":"W. Benton","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Biologics and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa Kyung","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-4204","authenticated-orcid":false,"given":"Yuji","family":"Mishina","sequence":"additional","affiliation":[{"name":"Department of Biologics and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2632-0841","authenticated-orcid":false,"given":"Nan E.","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/dvdy.278","article-title":"Making and shaping endochondral and intramembranous bones","volume":"250","author":"Galea","year":"2021","journal-title":"Dev. Dyn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ydbio.2007.08.028","article-title":"Cell fate specification during calvarial bone and suture development","volume":"311","author":"Rice","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/ncb3139","article-title":"The suture provides a niche for mesenchymal stem cells of craniofacial bones","volume":"17","author":"Zhao","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"dmm049390","DOI":"10.1242\/dmm.049390","article-title":"The clinical manifestations, molecular mechanisms and treatment of craniosynostosis","volume":"15","author":"Stanton","year":"2022","journal-title":"Dis. Models Mech."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/SCS.0000000000007035","article-title":"Updated Guideline on Treatment and Management of Craniosynostosis","volume":"32","author":"Mathijssen","year":"2021","journal-title":"J. Craniofacial Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.1469-7580.2005.00475.x","article-title":"Growth of the normal skull vault and its alteration in craniosynostosis: Insights from human genetics and experimental studies","volume":"207","author":"Wilkie","year":"2005","journal-title":"J. Anat."},{"key":"ref_7","unstructured":"Betances, E.M., Mendez, M.D., and Das, J.M. (2025). Craniosynostosis. StatPearls, StatPearls Publishing."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/ajmg.a.32106","article-title":"Priorities for public health research on craniosynostosis: Summary and recommendations from a Centers for Disease Control and Prevention-sponsored meeting","volume":"146","author":"Rasmussen","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/ajmg.a.32208","article-title":"A population-based study of craniosynostosis in metropolitan Atlanta, 1989\u20132003","volume":"146","author":"Boulet","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.wneu.2022.05.093","article-title":"Global Epidemiology of Craniosynostosis: A Systematic Review and Meta-Analysis","volume":"164","author":"Shlobin","year":"2022","journal-title":"World Neurosurg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1S","DOI":"10.1597\/11-138","article-title":"Parameters of care for craniosynostosis","volume":"49","author":"McCarthy","year":"2012","journal-title":"Cleft Palate-Craniofacial J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1097\/SCS.0b013e31824e26d6","article-title":"Analysis of morbidity and mortality in surgical management of craniosynostosis","volume":"23","author":"Lee","year":"2012","journal-title":"J. Craniofacial Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3171\/2009.8.PEDS09227","article-title":"A single-center experience with symptomatic postoperative calvarial growth restriction after extended strip craniectomy for sagittal craniosynostosis","volume":"5","author":"Adamo","year":"2010","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s003810050043","article-title":"Visual failure caused by raised intracranial pressure in craniosynostosis","volume":"13","author":"Stavrou","year":"1997","journal-title":"Childs Nerv. Syst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1097\/PRS.0b013e3182412a50","article-title":"Parameters of care for craniosynostosis: Craniofacial and neurologic surgery perspectives","volume":"129","author":"Warren","year":"2012","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3171\/2014.11.PEDS1426","article-title":"The incidence of raised intracranial pressure in nonsyndromic sagittal craniosynostosis following primary surgery","volume":"15","author":"Thomas","year":"2015","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E6","DOI":"10.3171\/2015.2.FOCUS14853","article-title":"Intracranial hypertension after surgical correction for craniosynostosis: A systematic review","volume":"38","author":"Christian","year":"2015","journal-title":"Neurosurg. Focus"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/SCS.0b013e3181f6c2fb","article-title":"An Epidemiological Study of Nonsyndromal Craniosynostoses","volume":"22","author":"Kolar","year":"2011","journal-title":"J. Craniofacial Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1089\/ten.teb.2021.0012","article-title":"Highlights on Advancing Frontiers in Tissue Engineering","volume":"28","author":"Ashammakhi","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2018.10.016","article-title":"Pore size directs bone marrow stromal cell fate and tissue regeneration in nanofibrous macroporous scaffolds by mediating vascularization","volume":"82","author":"Gupte","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Swanson, W.B., Omi, M., Woodbury, S.M., Douglas, L.M., Eberle, M., Ma, P.X., Hatch, N.E., and Mishina, Y. (2022). Scaffold Pore Curvature Influences MuSC Fate through Differential Cellular Organization and YAP\/TAZ Activity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094499"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120769","DOI":"10.1016\/j.biomaterials.2021.120769","article-title":"Macropore design of tissue engineering scaffolds regulates mesenchymal stem cell differentiation fate","volume":"272","author":"Swanson","year":"2021","journal-title":"Biomaterials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cej.2018.01.010","article-title":"Biocompatibility, biodegradation and excretion of polylactic acid (PLA) in medical implants and theranostic systems","volume":"340","author":"Kaduri","year":"2018","journal-title":"Chem. Eng. J."},{"key":"ref_24","unstructured":"Hagan, C. (2025, January 25). When Are Mice Considered Old?. Available online: https:\/\/www.jax.org\/news-and-insights\/jax-blog\/2017\/november\/when-are-mice-considered-old."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Nam, H.K., Crouch, S., and Hatch, N.E. (2021). Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031140"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00223-013-9701-2","article-title":"Further analysis of the Crouzon mouse: Effects of the FGFR2(C342Y) mutation are cranial bone-dependent","volume":"92","author":"Liu","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70e","DOI":"10.1097\/01.prs.0000299393.36063.de","article-title":"Recurrence of synostosis following surgical repair of craniosynostosis","volume":"121","author":"Foster","year":"2008","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2020.11.037","article-title":"Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis","volume":"184","author":"Yu","year":"2021","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1038\/s41467-021-24801-6","article-title":"Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis","volume":"12","author":"Menon","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_30","first-page":"424","article-title":"Actual concepts in scaphocephaly: (An experience of 98 cases)","volume":"4","author":"Ciurea","year":"2011","journal-title":"J. Med. Life"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/4\/420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:40:22Z","timestamp":1775277622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/4\/420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["bioengineering13040420"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13040420","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]}}}