title: Cerium Oxide Nanoparticle Modified Scaffold Interface Enhances Vascularization of Bone Grafts by Activating Calcium Channel of Mesenchymal Stem Cells.
abstract: Insufficient blood perfusion is one of the critical problems that hamper the clinical application of tissue engineering bone (TEB). Current methods for improving blood vessel distribution in TEB mainly rely on delivering exogenous angiogenic factors to promote the proliferation, migration, differentiation, and vessel formation of endothelial cells (ECs) and/or endothelial progenitor cells (EPCs). However, obstacles including limited activity preservation, difficulty in controlled release, and high cost obstructed the practical application of this strategy. In this study, TEB scaffold were modified with cerium oxide nanoparticles (CNPs) and the effects of CNPs existed at the scaffold surface on the growth and paracrine behavior of mesenchymal stem cells (MSCs) were investigated. The CNPs could improve the proliferation and inhibit the apoptosis of MSCs. Meanwhile, the interaction between the cell membrane and the nanoparticle surface could activate the calcium channel of MSCs leading to the rise of intracellular free Ca(2+) level, which subsequently augments the stability of HIF-1α. These chain reactions finally resulted in high expression of angiogenic factor VEGF. The improved paracrine of VEGF could thereby promote the proliferation, differentiation, and tube formation ability of EPCs. Most importantly, in vivo ectopic bone formation experiment demonstrated this method could significantly improve the blood vessel distribution inside of TEB.
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chemistry, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Ce
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University , Chongqing 400038, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kang
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.|China Orthopedic Regenerative Medicine Group , Chongqing 400038, China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University , Chongqing 400038, China.
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D016025:Bone Transplantation / Q000379:methods*; D015220:Calcium Channels / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002563:Cerium / Q000008:administration & dosage / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects; D006025:Glycosaminoglycans; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D015220:Calcium Channels; D006025:Glycosaminoglycans; D002563:Cerium; C030583:ceric oxide; C007858:glucuronyl glucosamine glycan sulfate
keywords: angiogenesis; cerium oxide nanoparticles; mesenchymal stem cells; tissue engineering bone; vasculogenesis