Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways

Detalhes bibliográficos
Autor(a) principal: Helaehil, Júlia Venturini
Data de Publicação: 2025
Outros Autores: Huang, Boyang, Bartolo, Paulo, Santamaria-JR, Milton [UNESP], Caetano, Guilherme Ferreira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.injury.2025.112158
https://hdl.handle.net/11449/298625
Resumo: The repair of critical-sized bone defects represents significant clinical challenge. An alternative approach is the use of 3D composite scaffolds to support bone regeneration. Hydroxyapatite (HA) and tri-calcium phosphate (β-TCP), combined with polycaprolactone (PCL), offer promising mechanical resistance and biocompatibility. Bioelectrical stimulation (ES) at physiological levels is proposed to reestablishes tissue bioeletrocity and modulates cell signaling communication, such as the BMP/TGF-β and the RANK/RANK-L/OPG pathways. This study aimed to evaluate the use HA/TCP scaffolds and ES therapy for bone regeneration and their impact on the TGF-β/BMP pathway, alongside their relationship with the RANK/RANKL/OPG pathway in critical bone defects. The scaffolds were implanted at the bone defect in animal model (calvarial bone) and the area was subjected to ES application twice a week at 10 µA intensity of current for 5 min each session. Samples were collected for histomorphometry, immunohistochemistry, and molecular analysis. The TGF-β/BMP pathway study showed the HA/TCP+ES group increased BMP-7 gene expression at 30 and 60 days, and also greater endothelial vascular formation. Moreover, the HA/TCP and HA/TCP+ES groups exhibited a bone remodeling profile, indicated by RANKL/OPG ratio. HA/TCP scaffolds with ES enhanced vascular formation and mineralization initially, while modulation of the BMP/TGF pathway maintained bone homeostasis, controlling resorption via ES with HA/TCP.
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spelling Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathwaysBioprintingElectrical stimulationMicrocurrentTGF pathwayTissue engineeringThe repair of critical-sized bone defects represents significant clinical challenge. An alternative approach is the use of 3D composite scaffolds to support bone regeneration. Hydroxyapatite (HA) and tri-calcium phosphate (β-TCP), combined with polycaprolactone (PCL), offer promising mechanical resistance and biocompatibility. Bioelectrical stimulation (ES) at physiological levels is proposed to reestablishes tissue bioeletrocity and modulates cell signaling communication, such as the BMP/TGF-β and the RANK/RANK-L/OPG pathways. This study aimed to evaluate the use HA/TCP scaffolds and ES therapy for bone regeneration and their impact on the TGF-β/BMP pathway, alongside their relationship with the RANK/RANKL/OPG pathway in critical bone defects. The scaffolds were implanted at the bone defect in animal model (calvarial bone) and the area was subjected to ES application twice a week at 10 µA intensity of current for 5 min each session. Samples were collected for histomorphometry, immunohistochemistry, and molecular analysis. The TGF-β/BMP pathway study showed the HA/TCP+ES group increased BMP-7 gene expression at 30 and 60 days, and also greater endothelial vascular formation. Moreover, the HA/TCP and HA/TCP+ES groups exhibited a bone remodeling profile, indicated by RANKL/OPG ratio. HA/TCP scaffolds with ES enhanced vascular formation and mineralization initially, while modulation of the BMP/TGF pathway maintained bone homeostasis, controlling resorption via ES with HA/TCP.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)University Center of Hermínio Ometto Foundation FHO, Araras 13607-339, SPDivision of Dermatology Department of Internal Medicine Ribeirao Preto Medical School University of Sao Paulo, 05508-060Singapore Centre for 3D Printing School of Mechanical and Aerospace Engineering Nanyang Technological UniversityGraduate Program of Orthodontics University Center of Hermínio Ometto Foundation FHO, Araras 13607-339, SPDepartment of Social and Pediatric Dentistry Institute of Science and Technology São Paulo State University - Unesp, São José dos Campos, 12245-000Department of Social and Pediatric Dentistry Institute of Science and Technology São Paulo State University - Unesp, São José dos Campos, 12245-000FAPESP: 2018/21167–4CNPq: 423710/2018-4FHOUniversidade de São Paulo (USP)Nanyang Technological UniversityUniversidade Estadual Paulista (UNESP)Helaehil, Júlia VenturiniHuang, BoyangBartolo, PauloSantamaria-JR, Milton [UNESP]Caetano, Guilherme Ferreira2025-04-29T18:37:39Z2025-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.injury.2025.112158Injury, v. 56, n. 2, 2025.1879-02670020-1383https://hdl.handle.net/11449/29862510.1016/j.injury.2025.1121582-s2.0-85215101244Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInjuryinfo:eu-repo/semantics/openAccess2025-04-30T14:24:04Zoai:repositorio.unesp.br:11449/298625Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-04-30T14:24:04Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
title Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
spellingShingle Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
Helaehil, Júlia Venturini
Bioprinting
Electrical stimulation
Microcurrent
TGF pathway
Tissue engineering
title_short Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
title_full Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
title_fullStr Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
title_full_unstemmed Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
title_sort Bone regeneration: The influence of composite HA/TCP scaffolds and electrical stimulation on TGF/BMP and RANK/RANKL/OPG pathways
author Helaehil, Júlia Venturini
author_facet Helaehil, Júlia Venturini
Huang, Boyang
Bartolo, Paulo
Santamaria-JR, Milton [UNESP]
Caetano, Guilherme Ferreira
author_role author
author2 Huang, Boyang
Bartolo, Paulo
Santamaria-JR, Milton [UNESP]
Caetano, Guilherme Ferreira
author2_role author
author
author
author
dc.contributor.none.fl_str_mv FHO
Universidade de São Paulo (USP)
Nanyang Technological University
Universidade Estadual Paulista (UNESP)
dc.contributor.author.fl_str_mv Helaehil, Júlia Venturini
Huang, Boyang
Bartolo, Paulo
Santamaria-JR, Milton [UNESP]
Caetano, Guilherme Ferreira
dc.subject.por.fl_str_mv Bioprinting
Electrical stimulation
Microcurrent
TGF pathway
Tissue engineering
topic Bioprinting
Electrical stimulation
Microcurrent
TGF pathway
Tissue engineering
description The repair of critical-sized bone defects represents significant clinical challenge. An alternative approach is the use of 3D composite scaffolds to support bone regeneration. Hydroxyapatite (HA) and tri-calcium phosphate (β-TCP), combined with polycaprolactone (PCL), offer promising mechanical resistance and biocompatibility. Bioelectrical stimulation (ES) at physiological levels is proposed to reestablishes tissue bioeletrocity and modulates cell signaling communication, such as the BMP/TGF-β and the RANK/RANK-L/OPG pathways. This study aimed to evaluate the use HA/TCP scaffolds and ES therapy for bone regeneration and their impact on the TGF-β/BMP pathway, alongside their relationship with the RANK/RANKL/OPG pathway in critical bone defects. The scaffolds were implanted at the bone defect in animal model (calvarial bone) and the area was subjected to ES application twice a week at 10 µA intensity of current for 5 min each session. Samples were collected for histomorphometry, immunohistochemistry, and molecular analysis. The TGF-β/BMP pathway study showed the HA/TCP+ES group increased BMP-7 gene expression at 30 and 60 days, and also greater endothelial vascular formation. Moreover, the HA/TCP and HA/TCP+ES groups exhibited a bone remodeling profile, indicated by RANKL/OPG ratio. HA/TCP scaffolds with ES enhanced vascular formation and mineralization initially, while modulation of the BMP/TGF pathway maintained bone homeostasis, controlling resorption via ES with HA/TCP.
publishDate 2025
dc.date.none.fl_str_mv 2025-04-29T18:37:39Z
2025-02-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.injury.2025.112158
Injury, v. 56, n. 2, 2025.
1879-0267
0020-1383
https://hdl.handle.net/11449/298625
10.1016/j.injury.2025.112158
2-s2.0-85215101244
url http://dx.doi.org/10.1016/j.injury.2025.112158
https://hdl.handle.net/11449/298625
identifier_str_mv Injury, v. 56, n. 2, 2025.
1879-0267
0020-1383
10.1016/j.injury.2025.112158
2-s2.0-85215101244
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Injury
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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