3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering

Ilya Y. Bozo^1,2, Roman V. Deev^2,3, Igor V. Smirnov⁴, Alexander Yu. Fedotov⁴, Vladimir K. Popov⁵, Anton V. Mironov⁵, Olga A. Mironova⁵, Alexander Yu. Gerasimenko^6,7, Vladimir S. Komlev^4,5*

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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 Sciencen 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

IJB 2020, 6(3), 275 https://doi.org/10.18063/ijb.v6i3.275

© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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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.

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