Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Yun Liu,1,* Li-Zhi Deng,2,3,* Hai-Peng Sun,1 Jia-Yun Xu,1 Yi-Ming Li,1 Xin Xie,1 Li-Ming Zhang,2,3 Fei-Long Deng1 1Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of C...

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Autores principales: Liu Y, Deng LZ, Sun HP, Xu JY, Li YM, Xie X, Zhang LM, Deng FL
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Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:841d6b90a9ae43099281939a2e6223782021-12-02T05:03:00ZSustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis1178-2013https://doaj.org/article/841d6b90a9ae43099281939a2e6223782016-03-01T00:00:00Zhttps://www.dovepress.com/sustained-dual-release-of-placental-growth-factor-2-and-bone-morphogen-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yun Liu,1,* Li-Zhi Deng,2,3,* Hai-Peng Sun,1 Jia-Yun Xu,1 Yi-Ming Li,1 Xin Xie,1 Li-Ming Zhang,2,3 Fei-Long Deng1 1Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2PCFM Lab, 3GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods: Three groups of PlGF-2/BMP-2-loaded heparin–N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 µg PlGF-2; with 1.0 µg BMP-2; and with 0.5 µg PlGF-2 combined with 1.0 µg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results: The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion: PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone. Keywords: placental growth factor-2, bone morphogenic protein-2, heparin, nanocomplexes, osteogenesisLiu YDeng LZSun HPXu JYLi YMXie XZhang LMDeng FLDove Medical Pressarticleplacental growth factor-2bone morphogenic protein-2heparinnanocomplexesosteogenesisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1147-1158 (2016)
institution DOAJ
collection DOAJ
language EN
topic placental growth factor-2
bone morphogenic protein-2
heparin
nanocomplexes
osteogenesis
Medicine (General)
R5-920
spellingShingle placental growth factor-2
bone morphogenic protein-2
heparin
nanocomplexes
osteogenesis
Medicine (General)
R5-920
Liu Y
Deng LZ
Sun HP
Xu JY
Li YM
Xie X
Zhang LM
Deng FL
Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
description Yun Liu,1,* Li-Zhi Deng,2,3,* Hai-Peng Sun,1 Jia-Yun Xu,1 Yi-Ming Li,1 Xin Xie,1 Li-Ming Zhang,2,3 Fei-Long Deng1 1Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2PCFM Lab, 3GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods: Three groups of PlGF-2/BMP-2-loaded heparin–N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 µg PlGF-2; with 1.0 µg BMP-2; and with 0.5 µg PlGF-2 combined with 1.0 µg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results: The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion: PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone. Keywords: placental growth factor-2, bone morphogenic protein-2, heparin, nanocomplexes, osteogenesis
format article
author Liu Y
Deng LZ
Sun HP
Xu JY
Li YM
Xie X
Zhang LM
Deng FL
author_facet Liu Y
Deng LZ
Sun HP
Xu JY
Li YM
Xie X
Zhang LM
Deng FL
author_sort Liu Y
title Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
title_short Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
title_full Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
title_fullStr Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
title_full_unstemmed Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
title_sort sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/841d6b90a9ae43099281939a2e622378
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