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Osteoimmune Modulation and Guided Osteogenesis Promoted by Barrier Membranes Incorporated with S-Nitrosoglutathione (GSNO) and Mesenchymal Stem Cell-Derived Exosomes

Authors Wang X, Ao J, Lu H, Zhao Q, Ma Y, Zhang J, Ren H, Zhang Y

Received 7 February 2020

Accepted for publication 5 May 2020

Published 15 May 2020 Volume 2020:15 Pages 3483—3496

DOI https://doi.org/10.2147/IJN.S248741

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Xin Wang,1,2,* Jun Ao,1,* Haiping Lu,1 Qingyu Zhao,1 Yaping Ma,1,2 Jun Zhang,1 Hao Ren,3 Yi Zhang2,4

1Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China; 2Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China; 3Shenzhen Institute for Innovation and Translational Medicine, Shenzhen International Biological Valley-Life Science Industrial Park, Shenzhen, Guangdong 518119, People’s Republic of China; 4Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hao Ren
Shenzhen Institute for Innovation and Translational Medicine Shenzhen International Biological Valley-Life Science Industrial Park, Shenzhen 518119, Guangdong, People’s Republic of China
Tel +86 173 6972 4036
Fax +86 755-8420 0009
Email renhao0421@foxmail.com
Yi Zhang
Joint Orthopaedic Research Center of Zunyi Medical University & University of Rochester Medical Center (JCMR-ZMU & URMC), Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China
Tel +86 182 7566 2009
Fax +86 851-2860 9551
Email zhangyizmr@163.com

Background: The use of polycaprolactone (PCL) for bone defects in a clinical setting is limited due to a lack of bioactivity. Exosomes derived from mesenchymal stem cells (MSCs) have an important immunoregulatory potential and together with S-nitrosoglutathione (GSNO) they possess therapeutic potential for bone regeneration.
Materials and Methods: In this study, PCL was modified with GSNO and MSC-derived exosomes and the impact on macrophages and osteogenes is evaluated.
Results: MSC-derived exosomes exhibited a cup-shaped morphology and were internalized by macrophages and human bone marrow-derived mesenchymal stromal cells (hBMSCs). The pattern of internalization of scaffold-immobilized exosomes was similar in RAW264.7 cells and hBMSCs after 4h and 24h of co-culture. Assessment of macrophage morphology under inflammatory conditions by scanning electronic microscopy (SEM) and confocal microscopy demonstrated macrophages were significantly elongated and expression of pro-inflammatory genes markedly decreased when co-cultured with PCL/PDA + GSNO + exosome scaffolds. Furthermore, this scaffold modification significantly enhanced osteogenic differentiation of hBMSCs.
Discussion: This study demonstrated the possibility of using a GSNO- and exosome-based strategy to adapt barrier membrane scaffolds. PCL/PDA + GSNO + exosome scaffolds may serve as an important barrier membrane for osteogenesis and tissue regeneration.

Keywords: polycaprolactone, mesenchymal stem cells, exosomes, S-nitrosoglutathione, osteogenesis

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