title: Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering.
abstract: For the clinical application of bone tissue engineering with the combination of biomaterials and mesenchymal stem cells (MSCs), bone scaffolds should possess excellent biocompatibility and osteoinductivity to accelerate the repair of bone defects. Herein, strontium hydroxyapatite [SrHAP, Ca10-xSrx(PO4)6(OH)2]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different x values of 0, 1, 5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing x values from 0 to 10, the crystal cell volumes and axial lengths of SrHAP become gradually large because of the greater ion radius of Sr2+than Ca2+, while the crystal sizes of SrHAP decrease from 70.4nm to 46.7nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100-400μm, and the SrHAP nanocrystals are uniformly dispersed within the scaffolds. In vitro cell experiments reveal that all the HAP/CS, Sr1HAP/CS, Sr5HAP/CS and Sr10HAP/CS nanohybrid scaffolds possess excellent cytocompatibility with the favorable adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The Sr5HAP nanocrystals in the scaffolds do not affect the adhesion, spreading of hBMSCs, but they contribute remarkably to cell proliferation and osteogenic differentiation. As compared with the HAP/CS nanohybrid scaffold, the released Sr2+ions from the SrHAP/CS nanohybrid scaffolds enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and osteogenic-related COL-1 and ALP expression levels. Especially, the Sr5HAP/CS nanohybrid scaffolds exhibit the best osteoinductivity among four groups because of the synergetic effect between Ca2+and Sr2+ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for bone tissue engineering.
authors.affiliation: The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.
authors.forename: Qinfei
authors.initials: Q
authors.lastname: Ke
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China. Electronic address: zhangcq@sjtu.edu.cn.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China. Electronic address: ypguo@shnu.edu.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006882:Hydroxyapatites / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects; D010316:Particle Size; D013324:Strontium / Q000737:chemistry*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D006882:Hydroxyapatites; C076185:strontium hydroxyapatite; D048271:Chitosan; D000469:Alkaline Phosphatase; D013324:Strontium
keywords: Bone tissue engineering; Osteoinductivity; Porous scaffold; Strontium hydroxyapatite