International Journal of Nanomedicine (May 2020)

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

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

Journal volume & issue
Vol. Volume 15
pp. 3483 – 3496

Abstract

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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 workCorrespondence: Hao RenShenzhen Institute for Innovation and Translational Medicine Shenzhen International Biological Valley-Life Science Industrial Park, Shenzhen 518119, Guangdong, People’s Republic of ChinaTel +86 173 6972 4036Fax +86 755-8420 0009Email [email protected] ZhangJoint 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 ChinaTel +86 182 7566 2009Fax +86 851-2860 9551Email [email protected]: 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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