PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis

Objectives: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a te...

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Autores principales:	Wen-Xiang Cheng, Yan-Zhi Liu, Xiang-Bo Meng, Zheng-Tan Zheng, Ling-Li Li, Li-Qing Ke, Ling Li, Cui-Shan Huang, Guo-Yuan Zhu, Hu-Dan Pan, Ling Qin, Xin-Luan Wang, Peng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biomaterials Cucurbitacin B Angiogenesis Bone regeneration 3D printing Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/f6c87e271e144634bbd6573f90084d53
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spelling	oai:doaj.org-article:f6c87e271e144634bbd6573f90084d532021-11-04T04:30:53ZPLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis2214-031X10.1016/j.jot.2021.10.002https://doaj.org/article/f6c87e271e144634bbd6573f90084d532021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2214031X21000772https://doaj.org/toc/2214-031XObjectives: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. Methods: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and β-tricalcium phosphate (β-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. Results: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. Conclusion: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. The translational potential of this article: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.Wen-Xiang ChengYan-Zhi LiuXiang-Bo MengZheng-Tan ZhengLing-Li LiLi-Qing KeLing LiCui-Shan HuangGuo-Yuan ZhuHu-Dan PanLing QinXin-Luan WangPeng ZhangElsevierarticleBiomaterialsCucurbitacin BAngiogenesisBone regeneration3D printingDiseases of the musculoskeletal systemRC925-935ENJournal of Orthopaedic Translation, Vol 31, Iss , Pp 41-51 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biomaterials Cucurbitacin B Angiogenesis Bone regeneration 3D printing Diseases of the musculoskeletal system RC925-935
spellingShingle	Biomaterials Cucurbitacin B Angiogenesis Bone regeneration 3D printing Diseases of the musculoskeletal system RC925-935 Wen-Xiang Cheng Yan-Zhi Liu Xiang-Bo Meng Zheng-Tan Zheng Ling-Li Li Li-Qing Ke Ling Li Cui-Shan Huang Guo-Yuan Zhu Hu-Dan Pan Ling Qin Xin-Luan Wang Peng Zhang PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
description	Objectives: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. Methods: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and β-tricalcium phosphate (β-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. Results: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. Conclusion: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. The translational potential of this article: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.
format	article
author	Wen-Xiang Cheng Yan-Zhi Liu Xiang-Bo Meng Zheng-Tan Zheng Ling-Li Li Li-Qing Ke Ling Li Cui-Shan Huang Guo-Yuan Zhu Hu-Dan Pan Ling Qin Xin-Luan Wang Peng Zhang
author_facet	Wen-Xiang Cheng Yan-Zhi Liu Xiang-Bo Meng Zheng-Tan Zheng Ling-Li Li Li-Qing Ke Ling Li Cui-Shan Huang Guo-Yuan Zhu Hu-Dan Pan Ling Qin Xin-Luan Wang Peng Zhang
author_sort	Wen-Xiang Cheng
title	PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
title_short	PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
title_full	PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
title_fullStr	PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
title_full_unstemmed	PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
title_sort	plga/β-tcp composite scaffold incorporating cucurbitacin b promotes bone regeneration by inducing angiogenesis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f6c87e271e144634bbd6573f90084d53
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PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis

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