{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:10:45Z","timestamp":1789585845638,"version":"build-2803163510"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE029321"],"award-info":[{"award-number":["R01DE029321"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Each year, 1 in every 700 babies is born with an orofacial cleft in the USA. Despite a well-established protocol for early cleft repair, the alveolar cleft persists during craniofacial growth. Current surgical treatments with bone grafts for alveolar cleft often provide inadequate nasal base support and insufficient alveolar bone volume for permanent tooth eruption. Here, we developed 3-dimensionally printed polycaprolactone scaffolds with controlled delivery of icariin (ICA) to facilitate bone reconstruction. After establishing a reliable fabrication process, we determined the optimal loading dose and release kinetics of ICA for induced osteogenic differentiation of bone marrow mesenchymal stem\/progenitor cells and mineralized tissue formation in\u00a0vitro. Then, the ICA-releasing polycaprolactone scaffolds with the preoptimized dose were implanted into rats with full-thickness maxillary defects. Up to 8 weeks, micro-computed tomography analyses demonstrated significantly accelerated bone healing and defect closure with an ICA-releasing scaffold compared to scaffold alone and defect controls. Histology consistently confirmed the formation of dense woven bone with ICA-releasing scaffolds in contrast to unclosed gaps and soft tissue infiltration in controls. Our findings suggest the significant potential of ICA-releasing 3-dimensionally printed scaffolds to serve as a patient-focused and custom-built bone graft to improve the clinical outcome of alveolar cleft reconstruction.<\/jats:p>","DOI":"10.34133\/bmr.0199","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T08:06:56Z","timestamp":1746691616000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":6,"title":["Icariin-Releasing 3-Dimensionally Printed Scaffolds for Alveolar Cleft Reconstruction"],"prefix":"10.34133","volume":"29","author":[{"given":"Soomin","family":"Park","sequence":"first","affiliation":[{"name":"Center for Dental and Craniofacial Research, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander B.","family":"Pascal","sequence":"additional","affiliation":[{"name":"Section of Hospital Dentistry\/Division of Oral and Maxillofacial Surgery, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney B.","family":"Eisig","sequence":"additional","affiliation":[{"name":"Section of Hospital Dentistry\/Division of Oral and Maxillofacial Surgery, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Dental and Craniofacial Research, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hun Jin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Center for Dental and Craniofacial Research, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Dental and Craniofacial Research, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Zhang","sequence":"additional","affiliation":[{"name":"Veterinary Operations, Institute of Comparative Medicine (ICM), \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-1191","authenticated-orcid":true,"given":"Chang Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Dental and Craniofacial Research, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."},{"name":"Section of Hospital Dentistry\/Division of Oral and Maxillofacial Surgery, College of Dental Medicine, \rColumbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081603"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/22925503231203216"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coms.2020.01.001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/SAP.0000000000001682"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e318205f2b4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3171\/2021.3.FOCUS2152"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93951-w"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.939199"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00217"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matdes.2022.110659"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26545-8"},{"issue":"1","key":"e_1_3_3_14_2","article-title":"In situ tissue engineering of the tendon-to-bone interface by endogenous stem\/progenitor cells","volume":"12","author":"Tarafder S","year":"2020","unstructured":"Tarafder S, Brito JA, Minhas S, Effiong L, Thomopoulos S, Lee CH. In situ tissue engineering of the tendon-to-bone interface by endogenous stem\/progenitor cells. Biofabrication. 2020;12(1): Article 015008.","journal-title":"Biofabrication"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.05.039"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12185"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compositesb.2022.109625"},{"issue":"10","key":"e_1_3_3_18_2","first-page":"785","article-title":"Icariin enhances the osteogenic differentiation of bone marrow stromal cells but has no effects on the differentiation of newborn calvarial osteoblasts of rats","volume":"62","author":"Chen KM","year":"2007","unstructured":"Chen KM, Ma HP, Ge BF, Liu XY, Ma LP, Bai MH, Wang Y. Icariin enhances the osteogenic differentiation of bone marrow stromal cells but has no effects on the differentiation of newborn calvarial osteoblasts of rats. Pharmazie. 2007;62(10):785\u2013789.","journal-title":"Pharmazie"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2021.130961"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1416047"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2021.01.001"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.engreg.2025.01.001"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ad89fe"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/8\/2\/025003"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1138686"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200600442"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1597\/15-356"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.08.002"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.01.009"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181bf8024"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/2041731413517705"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11353"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2017.47.2.77"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13233-017-5134-5"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001665-200011010-00010"},{"key":"e_1_3_3_36_2","article-title":"Various manufacturing methods and ideal properties of scaffolds for tissue engineering applications","volume":"1","author":"Suamte L","year":"2023","unstructured":"Suamte L, Tirkey A, Barman J, Babu PJ. Various manufacturing methods and ideal properties of scaffolds for tissue engineering applications. Smart Mater Manufact. 2023;1: Article 100011.","journal-title":"Smart Mater Manufact"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-009-0367-0"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00455-007-9126-z"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/13.5.362"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(65)90060-9"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12541-022-00755-7"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compositesb.2021.109084"},{"issue":"3","key":"e_1_3_3_43_2","first-page":"50","article-title":"The effect of icariin on immunity and its potential application","volume":"7","author":"Shen R","year":"2018","unstructured":"Shen R, Wang JH. The effect of icariin on immunity and its potential application. Am J Clin Exp Immunol. 2018;7(3):50\u201356.","journal-title":"Am J Clin Exp Immunol"}],"container-title":["Biomaterials Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/bmr.0199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:00:48Z","timestamp":1748592048000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/bmr.0199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":42,"alternative-id":["10.34133\/bmr.0199"],"URL":"https:\/\/doi.org\/10.34133\/bmr.0199","relation":{},"ISSN":["2055-7124"],"issn-type":[{"value":"2055-7124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-25","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0199"}}