Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction

Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic te...

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Main Authors: Zhenyu Zhao, Huitong Ruan, Aopan Chen, Wei Xiong, Mingzhu Zhang, Ming Cai, Wenguo Cui
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2023-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0221
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author Zhenyu Zhao
Huitong Ruan
Aopan Chen
Wei Xiong
Mingzhu Zhang
Ming Cai
Wenguo Cui
author_facet Zhenyu Zhao
Huitong Ruan
Aopan Chen
Wei Xiong
Mingzhu Zhang
Ming Cai
Wenguo Cui
author_sort Zhenyu Zhao
collection DOAJ
description Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.
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spelling doaj.art-3cc149efb96e44b8b3288ef452abf8f22024-03-03T03:28:21ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742023-01-01610.34133/research.0221Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone ReconstructionZhenyu Zhao0Huitong Ruan1Aopan Chen2Wei Xiong3Mingzhu Zhang4Ming Cai5Wenguo Cui6Department of Orthopaedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No.301 Middle Yanchang Road, Shanghai 200072, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Department of Orthopaedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No.301 Middle Yanchang Road, Shanghai 200072, China.Department of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, 1 Dongjiao Minxiang, Beijing 100730, China.Department of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, 1 Dongjiao Minxiang, Beijing 100730, China.Department of Orthopaedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No.301 Middle Yanchang Road, Shanghai 200072, China.Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.https://spj.science.org/doi/10.34133/research.0221
spellingShingle Zhenyu Zhao
Huitong Ruan
Aopan Chen
Wei Xiong
Mingzhu Zhang
Ming Cai
Wenguo Cui
Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction
Research
title Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction
title_full Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction
title_fullStr Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction
title_full_unstemmed Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction
title_short Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction
title_sort genetic engineered ultrasound triggered injectable hydrogels for promoting bone reconstruction
url https://spj.science.org/doi/10.34133/research.0221
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