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ORIGINAL ARTICLE

3D Printed Gene-activated Octacalcium Phosphate

Implants for Large Bone Defects Engineering

Ilya Y. Bozo , Roman V. Deev , Igor V. Smirnov , Alexander Yu. Fedotov , Vladimir K. Popov ,
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Anton V. Mironov , Olga A. Mironova , Alexander Yu. Gerasimenko , Vladimir S. Komlev *
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1 Department of Maxillofacial Surgery, A.I. Burnazyan Federal Medical Biophysical Center, FMBA of Russia, Moscow, Russia
2 Research and Development Department, Human Stem Cells Institute, Moscow, Russia
3 Department of Pathology, I.I. Mechnikov North-Western State Medical University, Saint-Petersburg, Russia
4 A.A. Baikov Institute of Metallurgy and Materials Science, Russian Academy of Sciences, Moscow, Russia
5 Institute of Photon Technologies of Federal Scientific Research Centre “Crystallography and Photonics,” Russian Academy
of Sciences, Moscow, Russia
6 Institute for Bionic Technologies and Engineering, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
7 Institute of Biomedical Systems, National Research University of Electronic Technology, Moscow, Russia
Abstract: The aim of the study was the development of three-dimensional (3D) printed gene-activated implants based on
octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA. The first objective of the present work involved design and
fabrication of gene-activated bone substitutes based on the OCP and plasmid DNA with VEGFА gene using 3D printing approach
of ceramic constructs, providing the control of its architectonics compliance to the initial digital models. X-ray diffraction, scanning
electron microscopy (SEM), Fourier transform infrared spectroscopy, and compressive strength analyses were applied to investigate
the chemical composition, microstructure, and mechanical properties of the experimental samples. The biodegradation rate and
the efficacy of plasmid DNA delivery in vivo were assessed during standard tests with subcutaneous implantation to rodents in
the next stage. The final part of the study involved substitution of segmental tibia and mandibular defects in adult pigs with 3D
printed gene-activated implants. Biodegradation, osteointegration, and effectiveness of a reparative osteogenesis were evaluated
with computerized tomography, SEM, and a histological examination. The combination of gene therapy and 3D printed implants
manifested the significant clinical potential for effective bone regeneration in large/critical size defect cases.
Keywords: Three-dimensional printing, Bone tissue engineering, Calcium phosphate, Octacalcium phosphate, Gene, Plasmid
DNA, Vascular endothelial growth factor.

*Corresponding Author: Vladimir S. Komlev, A.A. Baikov Institute of Metallurgy and Materials Science, Russian Academy of Sciences,
Moscow, Russia; komlev@mail.ru

Received: March 10, 2020; Accepted: April 14, 2020; Published Online: June 03, 2020
(This article belongs to the Special Section: Bioprinting in Russia)
Citation: Bozo IY, Deev RV, Smirnov IV, et al., 2020 3D Printed Gene-activated Octacalcium Phosphate Implants for Large
Bone Defects Engineering. Int J Bioprint, 6(3): 275. DOI: 10.18063/ijb.v6i3.275.

1 Introduction and incrementally increasing . Despite the
[1]
development of numerous ordinary and activated
Skeletal bone disorder caused by traumas, bone substitutes, the management of large bone
inflammation, malignancies, intervertebral defects is still challenging and usually demands
disk disease, as well as alveolar ridge atrophy the use of bone autografts that is associated with
following tooth loss is highly prevalent a certain complication rate, donor site morbidity,

© 2020 Bozo, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International
License (http://creativecommons.org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the
original work is properly cited.
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