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Acceleration of Bone Regeneration in Bioactive Glass/Gelatin Composite Scaffolds Seeded With Bone Marrow-Derived Mesenchymal Stem Cells Over-Expressing Bone Morphogenetic Protein-7 Publisher Pubmed



Kargozar S1, 4 ; Hashemian SJ2, 3 ; Soleimani M4, 5 ; Milan PB4, 6 ; Askari M1 ; Khalaj V7 ; Samadikuchaksaraie A4, 6 ; Hamzehlou S8 ; Katebi AR9 ; Latifi N10 ; Mozafari M11 ; Baino F12
Authors
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Authors Affiliations
  1. 1. National Cell Bank Department, Pasteur Institute of Iran, Tehran, Iran
  2. 2. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Cellular and Molecular Research Center (CMRC), Iran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  7. 7. Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  8. 8. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Psychology, Allameh Tabatabai University, Tehran, Iran
  10. 10. Department of Plastic and Reconstructive Surgery, Hazrat Fatemeh Hospital, Iran University of Medical Sciences, Tehran, Iran
  11. 11. Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran
  12. 12. Institute of Materials Physics and Engineering, Department of Applied Science and Technology (DISAT), Politecnico di Torino, Torino, Italy

Source: Materials Science and Engineering C Published:2017


Abstract

In this research, the osteoinduction effect of a novel variant of bone morphogenetic protein-7 (BMP-7), delivered through bone marrow mesenchymal stem cells (BM-MSCs) seeded on bioactive glass/gelatin nanocomposite scaffolds, was evaluated in a calvarial critical size defect in rats. After being harvested and characterized in vitro, BM-MSCs were infected by a plasmid vector containing BMP-7 encoding gene enriched with a heparin-binding site (B2BMP-7) to assess its osteogenic effects in vivo. The animals were randomly categorized into three groups receiving the scaffold alone (group I), the scaffold seeded with BM-MSCs (group II), and the scaffold seeded with manipulated BM-MSCs (group III). After 2, 4 and 12 postoperative weeks, the animals were sacrificed and the harvested specimens were analyzed using histological and immunohistochemical staining. The results of in vitro tests (preliminary screening) showed that the synthesized scaffolds were biocompatible constructs supporting cell attachment and expansion. The in vivo results revealed higher osteogenesis in the defects filled with the B2BMP-7 excreting BM-MSCs/scaffolds compared to the other two groups. After 12 weeks of implantation, fully mature newly formed bone was detected throughout the damaged site, which indicates a synergistic effect of cells, scaffolds and growth factors in the process of tissue regeneration. Therefore, bioactive glass-containing scaffolds pre-seeded with manipulated BM-MSCs exhibit an effective combination to improve osteogenesis in bone defects, and the approach followed in this work could have a significant impact in the development of novel tissue engineering constructs. © 2017 Elsevier B.V.
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