{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T17:03:54Z","timestamp":1779987834496,"version":"3.53.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/15674\u20105"],"award-info":[{"award-number":["2016\/15674\u20105"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/00020\u20108"],"award-info":[{"award-number":["2019\/00020\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/13352\u20106"],"award-info":[{"award-number":["2020\/13352\u20106"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomed Mater Res"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bone regeneration in critical defects remains a clinical challenge, motivating the development of biomaterials capable of supporting osteogenesis and modulating local biological responses. This study investigated the regenerative potential of chitosan\u2013calcium (CH\u2013Ca) scaffolds functionalized with simvastatin (SV) in rat calvarial critical\u2010sized defects. Forty male Wistar rats were randomly assigned to four groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095 per group\/experimental period): SHAM (coagulum), Bio\u2010Oss (xenograft), CH\u2013Ca, and CH\u2013Ca\u2009+\u2009SV. Defects of 5\u2009mm were surgically created and filled according to group allocation. Animals were euthanized at 14 and 30\u2009days, and samples were processed for histological, histomorphometric, Picrosirius Red, and immunohistochemical (BMP\u20102 and osteocalcin [OCN]) analyses. Histologically, the SHAM group showed bone restricted to the defect margins with persistent inflammation, while Bio\u2010Oss exhibited partial bone extension and residual particles surrounded by connective tissue. In contrast, CH\u2013Ca and CH\u2013Ca\u2009+\u2009SV scaffolds supported linear bone formation progressing toward the defect center, with more pronounced mineralization in CH\u2013Ca\u2009+\u2009SV. Histomorphometry confirmed higher new bone formation (NBF%) in CH and CH\u2009+\u2009SV compared with SHAM and Bio\u2010Oss at both time points, with CH\u2009+\u2009SV surpassing CH at 30\u2009days. Picrosirius Red revealed greater collagen fiber maturation in CH\u2009+\u2009SV, whereas SHAM maintained a higher proportion of immature fibers. Immunohistochemistry demonstrated increased BMP\u20102 and OCN expression in CH and CH\u2009+\u2009SV, particularly in CH\u2009+\u2009SV, at both 14 and 30\u2009days. These findings indicate that SV\u2010loaded CH\u2013Ca scaffolds enhance bone regeneration by promoting osteogenesis, collagen maturation, and the expression of osteogenic proteins, suggesting their potential as a cost\u2010effective and biologically favorable strategy for the treatment of critical\u2010sized bone defects.\n                  <\/jats:p>","DOI":"10.1002\/jbm.b.70084","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T04:39:32Z","timestamp":1779856772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calcium\u2013Chitosan Scaffolds With Simvastatin Enhance Bone Regeneration in Critical\u2010Sized Calvarial Defects in Rats"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7929-1618","authenticated-orcid":false,"given":"Ruan Henrique Delmonica","family":"Barra","sequence":"first","affiliation":[{"name":"Department of Diagnostic and Surgery, Periodontics Division, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Nucleus of Study and Research in Periodontics and Implantology (NEPPI), School of Dentistry Sao Paulo State University (UNESP)  Aracatuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0618-2787","authenticated-orcid":false,"given":"Elisa Mara","family":"de Abreu Furquim","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, Periodontics Division, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Nucleus of Study and Research in Periodontics and Implantology (NEPPI), School of Dentistry Sao Paulo State University (UNESP)  Aracatuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edilson","family":"Ervolino","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, Periodontics Division, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Department of Basic Sciences, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-5980","authenticated-orcid":false,"given":"Henrique Rinaldi","family":"Matheus","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, Periodontics Division, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Discipline of Periodontics, School of Dentistry University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Bialon Carvalho","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, Periodontics Division, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Nucleus of Study and Research in Periodontics and Implantology (NEPPI), School of Dentistry Sao Paulo State University (UNESP)  Aracatuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"de Oliveira Gallinari","sequence":"additional","affiliation":[{"name":"Department of Operative Dentistry, Endodontics and Dental Materials, Scholl of Dentistry University of S\u00e3o Paulo (USP)  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1485-6104","authenticated-orcid":false,"given":"Diana Gabriela","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Operative Dentistry, Endodontics and Dental Materials, Scholl of Dentistry University of S\u00e3o Paulo (USP)  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-5747","authenticated-orcid":false,"given":"Juliano Milanezi","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, Periodontics Division, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Nucleus of Study and Research in Periodontics and Implantology (NEPPI), School of Dentistry Sao Paulo State University (UNESP)  Aracatuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.12645"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.27063"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.73.BJR-2017-0270.R1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2021.01.043"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40824-019-0157-y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202403641"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.4c01613"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031128"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-011-5942-5_7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/c4tb00027g"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.01.131"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.02.143"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515588885"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2012.07.005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216648022"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2015.10.014"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2018.02.014"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.34586"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211024207"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2024.153749"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.113"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20253"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040216"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-020-03234-5"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160716034"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-018-6129-2"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2002.73.10.1141"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223\u2010015\u20109981\u20109"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-813259-3.00005-1"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2015.05.002"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a031211"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.07.007"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.3c00609"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910233"}],"container-title":["Journal of Biomedical Materials Research Part B: Applied Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.b.70084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm.b.70084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.b.70084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T16:26:08Z","timestamp":1779985568000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.b.70084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jbm.b.70084"],"URL":"https:\/\/doi.org\/10.1002\/jbm.b.70084","archive":["Portico"],"relation":{},"ISSN":["1552-4973","1552-4981"],"issn-type":[{"value":"1552-4973","type":"print"},{"value":"1552-4981","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70084"}}