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Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3β pathway and facilitate bone repair in vivo

Authors Zhu DY, Lu B, Yin JH, Ke QF, Xu H, Zhang CQ, Guo YP, Gao YS

Received 6 November 2018

Accepted for publication 12 January 2019

Published 11 February 2019 Volume 2019:14 Pages 1085—1100

DOI https://doi.org/10.2147/IJN.S193576

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Dao-Yu Zhu,1,* Bin Lu,2,* Jun-Hui Yin,1 Qin-Fei Ke,2 He Xu,2 Chang-Qing Zhang,1 Ya-Ping Guo,2 You-Shui Gao1,3

1Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China; 3Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA 6009, Australia

*These authors contributed equally to this work

Background: Biomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known.
Methods: In this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects.
Results: The results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3β signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration.
Conclusion: Both in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering.

Keywords: bone scaffold, gadolinium, Akt/GSK3β pathway, bone regeneration


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