{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:00:09Z","timestamp":1778097609872,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2018\/21167-4"],"award-info":[{"award-number":["2018\/21167-4"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2016\/23237-4"],"award-info":[{"award-number":["2016\/23237-4"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["423710\/2018-4"],"award-info":[{"award-number":["423710\/2018-4"]}]},{"DOI":"10.13039\/501100003593","name":"CNPq (\u201cConselho Nacional do desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u201d)","doi-asserted-by":"publisher","award":["2018\/21167-4"],"award-info":[{"award-number":["2018\/21167-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq (\u201cConselho Nacional do desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u201d)","doi-asserted-by":"publisher","award":["2016\/23237-4"],"award-info":[{"award-number":["2016\/23237-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq (\u201cConselho Nacional do desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u201d)","doi-asserted-by":"publisher","award":["423710\/2018-4"],"award-info":[{"award-number":["423710\/2018-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Critical bone defects are the most difficult challenges in the area of tissue repair. Polycaprolactone (PCL) scaffolds, associated with hydroxyapatite (HA) and tricalcium phosphate (TCP), are reported to have an enhanced bioactivity. Moreover, the use of electrical stimulation (ES) has overcome the lack of bioelectricity at the bone defect site and compensated the endogenous electrical signals. Such treatments could modulate cells and tissue signaling pathways. However, there is no study investigating the effects of ES and bioceramic composite scaffolds on bone tissue formation, particularly in the view of cell signaling pathway. This study aims to investigate the application of HA\/TCP composite scaffolds and ES and their effects on the Wingless-related integration site (Wnt) pathway in critical bone repair. Critical bone defects (25 mm2) were performed in rats, which were divided into four groups: PCL, PCL + ES, HA\/TCP and HA\/TCP + ES. The scaffolds were grafted at the defect site and applied with the ES application twice a week using 10 \u00b5A of current for 5 min. Bone samples were collected for histomorphometry, immunohistochemistry and molecular analysis. At the Wnt canonical pathway, HA\/TCP and HA\/TCP + ES groups showed higher Wnt1 and \u03b2-catenin gene expression levels, especially HA\/TCP. Moreover, HA\/TCP + ES presented higher Runx2, Osterix and Bmp-2 levels. At the Wnt non-canonical pathway, HA\/TCP group showed higher voltage-gated calcium channel (Vgcc), calmodulin-dependent protein kinase II, and Wnt5a genes expression, while HA\/TCP + ES presented higher protein expression of VGCC and calmodulin (CaM) at the same period. The decrease in sclerostin and osteopontin genes expressions and the lower bone sialoprotein II in the HA\/TCP + ES group may be related to the early bone remodeling. This study shows that the use of ES modulated the Wnt pathways and accelerated the osteogenesis with improved tissue maturation.<\/jats:p>","DOI":"10.3390\/bioengineering10010075","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T07:05:09Z","timestamp":1673247909000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Electrical Stimulation Therapy and HA\/TCP Composite Scaffolds Modulate the Wnt Pathways in Bone Regeneration of Critical-Sized Defects"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4414-6998","authenticated-orcid":false,"given":"J\u00falia Venturini","family":"Helaehil","sequence":"first","affiliation":[{"name":"Graduate Program in Biomedical Sciences, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"}]},{"given":"Luiza Venturini","family":"Helaehil","sequence":"additional","affiliation":[{"name":"Graduate Program in Biomedical Sciences, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"}]},{"given":"Laryssa Fernanda","family":"Alves","sequence":"additional","affiliation":[{"name":"Graduate Program in Biomedical Sciences, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5669-349X","authenticated-orcid":false,"given":"Boyang","family":"Huang","sequence":"additional","affiliation":[{"name":"Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3490-5030","authenticated-orcid":false,"given":"Milton","family":"Santamaria-Jr","sequence":"additional","affiliation":[{"name":"Graduate Program in Biomedical Sciences, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"},{"name":"Graduate Program of Orthodontics, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-726X","authenticated-orcid":false,"given":"Paulo","family":"Bartolo","sequence":"additional","affiliation":[{"name":"Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-1080","authenticated-orcid":false,"given":"Guilherme Ferreira","family":"Caetano","sequence":"additional","affiliation":[{"name":"Graduate Program in Biomedical Sciences, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"},{"name":"Graduate Program of Orthodontics, University Center of Herm\u00ednio Ometto Foundation, FHO, Araras 13607-339, Brazil"},{"name":"Division of Dermatology, Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo 05508-060, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","first-page":"278","article-title":"3D bioactive composite scaffolds for bone tissue engineering","volume":"3","author":"Turnbull","year":"2018","journal-title":"Bioact. 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