, Volume 9, Issue 4, pp 909–917 | Cite as

Comparative Analysis of the Effect of Gene-Activated Grafts Carrying a PBUD-VEGF165A-BMP2 Plasmid on Bone Regeneration in a Rat Femur Defect Model

  • Margarita N. Zhuravleva
  • Marsel R. Khaliullin
  • Ruslan F. Masgutov
  • Ilya Y. Bozo
  • Albert A. RizvanovEmail author
  • Roman V. Deev


Delayed union and non-union are widespread complications of bone fracture healing which are worse in cases of concomitant chronic diseases (diabetes mellitus, alcoholism, etc.). Osteonecrosis of different etiology is another cause of persistent bone defects. In the current research, we tested gene-activated grafts (GAGs) carrying dual expression cassette plasmid constructs encoding human vascular endothelial growth factor A (VEGF-A) and bone morphogenetic protein 2 (BMP2) genes. We modeled a thighbone diaphyseal defect on male Wistar rats and tested either GAG based on collagen and hydroxyapatite granules (Collapol CP-3) or GAG octacalcium phosphate (OCP) grafts. Histological examination revealed significant increases in vascularization and bone tissue formation in the GAG Collapol CP-3 graft experimental group, while neither the OCP nor the GAG OCP group showed a positive effect on callus formation. We conclude that GAG Collapol CP-3 bone grafts are a potential therapeutic solution for bone tissue regeneration and further clinical studies are required.


Gene therapy Traumatology Plasmid Osteogenesis Angiogenesis Bone morphogenetic protein Vascular endothelial growth factor 



The work was performed according to the Russian Government Program of Competitive Growth of Kazan Federal University. Some of the experiments were conducted using the equipment of the Interdisciplinary Center for Collective Use of Kazan Federal University, Interdisciplinary Center for Analytical Microscopy, and Pharmaceutical Research and Education Center, Kazan (Volga region) Federal University, Kazan, Russia. Work was funded by the Grant of the President of the Russian Federation for state support of the leading scientific schools of the Russian Federation НШ-3076.2018.4. Albert A. Rizvanov was supported by state assignment 20.5175.2017/6.7 and 17.9783.2017/8.9 of the Ministry of Science and Higher Education of Russian Federation.

Compliance with Ethical Standards

In vivo experiments were approved by the Local Ethical Committee of Kazan Federal University (Protocol No. 3 dated 23 March 2017).

Conflict of Interest


Research Involving Humans and Animals Statement


Informed Consent


Funding Statement



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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Kazan Federal UniversityKazanRussia
  2. 2.A.I. Burnazyan Federal Medical Biophysical CenterFMBA of RussiaMoscowRussia
  3. 3.Histograft, LLCMoscowRussia
  4. 4.Ryazan State Medical UniversityRyazanRussia
  5. 5.Republican Clinical Hospital of the Ministry of Health of the Republic of TatarstanKazanRussia

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