title: Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways.
abstract: Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (α1, α2, β1 and β3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-κB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering.
authors.affiliation: Department of Oral and Maxillofacial Pathology & Research Center for tooth and periodontal tissue regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Oral and Maxillofacial Surgery, Guro Hospital, Korea University, Seoul, Republic of Korea.
authors.forename: Eui-Suk
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Pathology & Research Center for tooth and periodontal tissue regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Mi-joo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors.forename: Jung-Ju
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea.
authors.forename: Hae-Hyoung
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Pathology & Research Center for tooth and periodontal tissue regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Yi
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Pathology & Research Center for tooth and periodontal tissue regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Eun-cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008280:Magnetics; D053761:Nanocomposites; D009805:Odontogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D016023:Integrins