{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:39:11Z","timestamp":1790674751003,"version":"4.1.0"},"reference-count":57,"publisher":"SAGE Publications","issue":"23-24","license":[{"start":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T00:00:00Z","timestamp":1476748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part A"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>\n                    Hedgehog (Hh) signaling positively regulates both endochondral and intramembranous ossification. Use of small molecules for tissue engineering applications poses several advantages. In this study, we examined whether use of an acellular scaffold treated with the small molecule Smoothened agonist (SAG) could aid in critical-size mouse calvarial defect repair. First, we verified the pro-osteogenic effect of SAG\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    , using primary neonatal mouse calvarial cells (NMCCs). Next, a 4\u2009mm nonhealing defect was created in the mid-parietal bone of 10-week-old CD-1 mice. The scaffold consisted of a custom-fabricated poly(lactic-co-glycolic acid) disc with hydroxyapatite coating (measuring 4\u2009mm diameter\u2009\u00d7\u20090.5\u2009mm thickness). Treatment groups included dimethylsulfoxide control (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20096), 0.5\u2009mM SAG (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20097) or 1.0\u2009mM SAG (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20097). Evaluation was performed at 4 and 8 weeks postoperative, by a combination of high-resolution microcomputed tomography, histology (H &amp; E, Masson's Trichrome), histomorphometry, and immunohistochemistry (BSP, OCN, VEGF).\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    results showed that SAG treatment induced a significant and dose-dependent increase in calvarial bone healing by all radiographic parameters. Histomorphometric analysis showed an increase in all parameters of bone formation with SAG treatment, but also an increase in blood vessel number and density. In summary, SAG is a pro-osteogenic, provasculogenic stimulus when applied locally in a bone defect environment.\n                  <\/jats:p>","DOI":"10.1089\/ten.tea.2016.0167","type":"journal-article","created":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T06:34:30Z","timestamp":1475649270000},"page":"1357-1366","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Calvarial Defect Healing Induced by Small Molecule Smoothened Agonist"],"prefix":"10.1177","volume":"22","author":[{"given":"Soonchul","family":"Lee","sequence":"first","affiliation":[{"name":"University of California"},{"name":"CHA University"},{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shen","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin Chuan","family":"Pan","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Shrestha","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Asatrian","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Meyers","sequence":"additional","affiliation":[{"name":"Johns Hopkins University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lee","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia","family":"Soo","sequence":"additional","affiliation":[{"name":"University of California"},{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Ting","sequence":"additional","affiliation":[{"name":"CHA University"},{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron W.","family":"James","sequence":"additional","affiliation":[{"name":"University of California"},{"name":"Johns Hopkins University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,10,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199810001-00003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2005.07.029"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_1993_030_0579_sotica_2.3.co_2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-198912000-00009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0030-5898(05)70120-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.88.2.0255"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2012.0519"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2015.0357"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.347716"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00061"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.01.033"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10166"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00014-8"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7156"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.11.2085"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02214-05"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0048"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2011.0461"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.07.004"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.05.096"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182542899"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-4924-1-10"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139740"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.409342"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.04.016"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.267"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e31817747b5"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181e5f81a"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007120"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181e5f892"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011177"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2013.05.023"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.07.046"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/54\/7\/020"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.113"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0705"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1197"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(00)00006-1"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.09.005"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005843"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20768"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.16.2072"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2010.0250"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.03.089"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0555"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.10.011"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/71875"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.133"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.3171\/2009.1.SPINE08473"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl476"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.2217\/rme.12.33"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2013.12.002"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319190007"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2005.06.006"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-12-43"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.01.012"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.12.1903"}],"container-title":["Tissue Engineering Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ten.tea.2016.0167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ten.tea.2016.0167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ten.tea.2016.0167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:46:31Z","timestamp":1777697191000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/ten.tea.2016.0167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,18]]},"references-count":57,"journal-issue":{"issue":"23-24","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1089\/ten.tea.2016.0167"],"URL":"https:\/\/doi.org\/10.1089\/ten.tea.2016.0167","relation":{},"ISSN":["1937-3341","1937-335X"],"issn-type":[{"value":"1937-3341","type":"print"},{"value":"1937-335X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,18]]}}}