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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: Cheng, Wen-Xiang, Liu, Yan-Zhi, Meng, Xiang-Bo, Zheng, Zheng-Tan, Li, Ling-Li, Ke, Li-Qing, Li, Ling, Huang, Cui-Shan, Zhu, Guo-Yuan, Pan, Hu-Dan, Qin, Ling, Wang, Xin-Luan, Zhang, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Speaking Orthopaedic Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571783/
https://www.ncbi.nlm.nih.gov/pubmed/34804799
http://dx.doi.org/10.1016/j.jot.2021.10.002
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author Cheng, Wen-Xiang
Liu, Yan-Zhi
Meng, Xiang-Bo
Zheng, Zheng-Tan
Li, Ling-Li
Ke, Li-Qing
Li, Ling
Huang, Cui-Shan
Zhu, Guo-Yuan
Pan, Hu-Dan
Qin, Ling
Wang, Xin-Luan
Zhang, Peng
author_facet Cheng, Wen-Xiang
Liu, Yan-Zhi
Meng, Xiang-Bo
Zheng, Zheng-Tan
Li, Ling-Li
Ke, Li-Qing
Li, Ling
Huang, Cui-Shan
Zhu, Guo-Yuan
Pan, Hu-Dan
Qin, Ling
Wang, Xin-Luan
Zhang, Peng
author_sort Cheng, Wen-Xiang
collection PubMed
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.
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spelling pubmed-85717832021-11-18 PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis Cheng, Wen-Xiang Liu, Yan-Zhi Meng, Xiang-Bo Zheng, Zheng-Tan Li, Ling-Li Ke, Li-Qing Li, Ling Huang, Cui-Shan Zhu, Guo-Yuan Pan, Hu-Dan Qin, Ling Wang, Xin-Luan Zhang, Peng J Orthop Translat Original Article 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. Chinese Speaking Orthopaedic Society 2021-11-01 /pmc/articles/PMC8571783/ /pubmed/34804799 http://dx.doi.org/10.1016/j.jot.2021.10.002 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Cheng, Wen-Xiang
Liu, Yan-Zhi
Meng, Xiang-Bo
Zheng, Zheng-Tan
Li, Ling-Li
Ke, Li-Qing
Li, Ling
Huang, Cui-Shan
Zhu, Guo-Yuan
Pan, Hu-Dan
Qin, Ling
Wang, Xin-Luan
Zhang, Peng
PLGA/β-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis
title 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_short 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571783/
https://www.ncbi.nlm.nih.gov/pubmed/34804799
http://dx.doi.org/10.1016/j.jot.2021.10.002
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