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Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system

The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via g...

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Autores principales: Liu, Zheng, Xu, Zhenchao, Wang, Xiyang, Zhang, Yilu, Wu, Yunqi, Jiang, Dingyu, Jia, Runze
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634119/
https://www.ncbi.nlm.nih.gov/pubmed/36338136
http://dx.doi.org/10.3389/fbioe.2022.1028278
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author Liu, Zheng
Xu, Zhenchao
Wang, Xiyang
Zhang, Yilu
Wu, Yunqi
Jiang, Dingyu
Jia, Runze
author_facet Liu, Zheng
Xu, Zhenchao
Wang, Xiyang
Zhang, Yilu
Wu, Yunqi
Jiang, Dingyu
Jia, Runze
author_sort Liu, Zheng
collection PubMed
description The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro. Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo. The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation (p < 0.05) compared to pure titanium alloy scaffolds in vitro. Furthermore, the composite scaffold can exhibit significant osteogenic differentiation (p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds (p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups (p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration.
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spelling pubmed-96341192022-11-05 Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system Liu, Zheng Xu, Zhenchao Wang, Xiyang Zhang, Yilu Wu, Yunqi Jiang, Dingyu Jia, Runze Front Bioeng Biotechnol Bioengineering and Biotechnology The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro. Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo. The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation (p < 0.05) compared to pure titanium alloy scaffolds in vitro. Furthermore, the composite scaffold can exhibit significant osteogenic differentiation (p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds (p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups (p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration. Frontiers Media S.A. 2022-10-21 /pmc/articles/PMC9634119/ /pubmed/36338136 http://dx.doi.org/10.3389/fbioe.2022.1028278 Text en Copyright © 2022 Liu, Xu, Wang, Zhang, Wu, Jiang and Jia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Liu, Zheng
Xu, Zhenchao
Wang, Xiyang
Zhang, Yilu
Wu, Yunqi
Jiang, Dingyu
Jia, Runze
Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system
title Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system
title_full Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system
title_fullStr Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system
title_full_unstemmed Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system
title_short Construction and osteogenic effects of 3D-printed porous titanium alloy loaded with VEGF/BMP-2 shell-core microspheres in a sustained-release system
title_sort construction and osteogenic effects of 3d-printed porous titanium alloy loaded with vegf/bmp-2 shell-core microspheres in a sustained-release system
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634119/
https://www.ncbi.nlm.nih.gov/pubmed/36338136
http://dx.doi.org/10.3389/fbioe.2022.1028278
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