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New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis

OBJECTIVES: Large bone defect repair is a challenging clinical problem due to limited self-repair ability. A well-designed bone filling product should possess the ability to induce tissue in-growth and facilitate neovascularization and new bone formation. Puerarin has been used in clinics for a long...

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Autores principales: Cao, Huijuan, Li, Lingli, Li, Ling, Meng, Xiangbo, Liu, Yanzhi, Cheng, Wenxiang, Zhang, Peng, Gao, Yongbo, Qin, Ling, Wang, Xinluan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Speaking Orthopaedic Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352809/
https://www.ncbi.nlm.nih.gov/pubmed/35979175
http://dx.doi.org/10.1016/j.jot.2022.05.003
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author Cao, Huijuan
Li, Lingli
Li, Ling
Meng, Xiangbo
Liu, Yanzhi
Cheng, Wenxiang
Zhang, Peng
Gao, Yongbo
Qin, Ling
Wang, Xinluan
author_facet Cao, Huijuan
Li, Lingli
Li, Ling
Meng, Xiangbo
Liu, Yanzhi
Cheng, Wenxiang
Zhang, Peng
Gao, Yongbo
Qin, Ling
Wang, Xinluan
author_sort Cao, Huijuan
collection PubMed
description OBJECTIVES: Large bone defect repair is a challenging clinical problem due to limited self-repair ability. A well-designed bone filling product should possess the ability to induce tissue in-growth and facilitate neovascularization and new bone formation. Puerarin has been used in clinics for a long time, and recently it was found to be able to promote osteogenesis. This study aimed to investigate a puerarin-based drug/delivery combination implant for promoting large bone defect repair. METHODS: Puerarin was incorporated into the poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP, PT) to form a porous PLGA/TCP/Puerarin (PTP) composite scaffold by low-temperature rapid prototyping technology. Its structural and degradation were analyzed in vitro. Then we employed a rat calvarial critical size defect model to assess the potency of the PTP scaffold. MC3T3-E1 cells and EA. hy 926 ​cells were used to investigate the underlying mechanism. RESULTS: PTP scaffold inherited all advantages of PT scaffold in structural, mechanical, and biodegradation, meanwhile puerarin stably and continuously released from PTP scaffold and lasted for 5 months in vitro. At 8 weeks after implantation, the PTP scaffold triggered new bone formation in the macro-pores of the scaffold and inside the scaffold accompanied by the degrading materials. The underlying mechanism revealed that the PTP scaffold induced vascular infiltration and recruit repair cells through stimulating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) expressions to promote angiogenesis and osteogenesis. CONCLUSION: Puerarin-enriched porous PTP scaffold was a promising local delivery system with sustained release of puerarin for facilitating defect repair through getting synergistic angiogenic and osteogenic effects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The PTP scaffold presents a potential drug/device combination medical implant for large bone defect repair, which also provides a new and innovative application for the “old drug” puerarin.
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spelling pubmed-93528092022-08-16 New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis Cao, Huijuan Li, Lingli Li, Ling Meng, Xiangbo Liu, Yanzhi Cheng, Wenxiang Zhang, Peng Gao, Yongbo Qin, Ling Wang, Xinluan J Orthop Translat Original Article OBJECTIVES: Large bone defect repair is a challenging clinical problem due to limited self-repair ability. A well-designed bone filling product should possess the ability to induce tissue in-growth and facilitate neovascularization and new bone formation. Puerarin has been used in clinics for a long time, and recently it was found to be able to promote osteogenesis. This study aimed to investigate a puerarin-based drug/delivery combination implant for promoting large bone defect repair. METHODS: Puerarin was incorporated into the poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP, PT) to form a porous PLGA/TCP/Puerarin (PTP) composite scaffold by low-temperature rapid prototyping technology. Its structural and degradation were analyzed in vitro. Then we employed a rat calvarial critical size defect model to assess the potency of the PTP scaffold. MC3T3-E1 cells and EA. hy 926 ​cells were used to investigate the underlying mechanism. RESULTS: PTP scaffold inherited all advantages of PT scaffold in structural, mechanical, and biodegradation, meanwhile puerarin stably and continuously released from PTP scaffold and lasted for 5 months in vitro. At 8 weeks after implantation, the PTP scaffold triggered new bone formation in the macro-pores of the scaffold and inside the scaffold accompanied by the degrading materials. The underlying mechanism revealed that the PTP scaffold induced vascular infiltration and recruit repair cells through stimulating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) expressions to promote angiogenesis and osteogenesis. CONCLUSION: Puerarin-enriched porous PTP scaffold was a promising local delivery system with sustained release of puerarin for facilitating defect repair through getting synergistic angiogenic and osteogenic effects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The PTP scaffold presents a potential drug/device combination medical implant for large bone defect repair, which also provides a new and innovative application for the “old drug” puerarin. Chinese Speaking Orthopaedic Society 2022-07-31 /pmc/articles/PMC9352809/ /pubmed/35979175 http://dx.doi.org/10.1016/j.jot.2022.05.003 Text en © 2022 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
Cao, Huijuan
Li, Lingli
Li, Ling
Meng, Xiangbo
Liu, Yanzhi
Cheng, Wenxiang
Zhang, Peng
Gao, Yongbo
Qin, Ling
Wang, Xinluan
New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
title New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
title_full New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
title_fullStr New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
title_full_unstemmed New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
title_short New use for old drug: Local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
title_sort new use for old drug: local delivery of puerarin facilitates critical-size defect repair in rats by promoting angiogenesis and osteogenesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352809/
https://www.ncbi.nlm.nih.gov/pubmed/35979175
http://dx.doi.org/10.1016/j.jot.2022.05.003
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