Development of a standardized and reproducible murine femoral distraction osteogenesis model

Objective: Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic...

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Main Authors: Yuejun Lin, Zhaowei Jiang, Jiaming Yang, Ming Wang, Haixing Wang, Xiaoting Zhang, Xuan Lu, Shanshan Bai, Tongzhou Liang, Botai Li, Jie Shao, Lu Zhang, Dashuang Gao, Jiajun Chen, Sien Lin, Fan Yang, Gang Li
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Journal of Orthopaedic Translation
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214031X24000871
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author Yuejun Lin
Zhaowei Jiang
Jiaming Yang
Ming Wang
Haixing Wang
Xiaoting Zhang
Xuan Lu
Shanshan Bai
Tongzhou Liang
Botai Li
Jie Shao
Lu Zhang
Dashuang Gao
Jiajun Chen
Sien Lin
Fan Yang
Gang Li
author_facet Yuejun Lin
Zhaowei Jiang
Jiaming Yang
Ming Wang
Haixing Wang
Xiaoting Zhang
Xuan Lu
Shanshan Bai
Tongzhou Liang
Botai Li
Jie Shao
Lu Zhang
Dashuang Gao
Jiajun Chen
Sien Lin
Fan Yang
Gang Li
author_sort Yuejun Lin
collection DOAJ
description Objective: Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model. Methods: A mini-titanium lengthener was designed and fabricated. The mini-lengthener was applied on the murine femur with four threaded pins using a designed clamp as the drilling and insertion guide. After transverse osteotomy using a Gigli saw, and after 5 days of latency, DO procedures started at 0.3 mm/day for 10 days, and the consolidation period was left for 28 days. The bone formation was monitored by radiography and histology. Potential effects on animal locomotion during DO were also measured by behavior tests. Results: Separated bone segments maintained good alignment during the entire DO phases. New bone formation was found as early as the end of the distraction phase. Active bone remodeling was found between the separated bone segments at late distraction and early consolidation phases. At the mature consolidation phase, bone remodeling was mainly observed in the contact cortical bone. Mice underwent DO procedure did not have significant impairment in their locomotion. Conclusion: We have successfully developed a murine femoral DO model, which may be used to study the biological processes of DO. We also developed the mini-lengthener and the guide clamp to ensure the standardization and reproducibility of the mouse DO model.The translational potential of this article: Current study reports the development of a murine femoral DO model. A well-established murine DO model will facilitate further investigations of the biological mechanisms of DO in various transgenic and normal mice.
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spelling doaj-art-b81ed7a7d99f48a6934be23d74c46bb92024-12-05T05:20:21ZengElsevierJournal of Orthopaedic Translation2214-031X2024-11-01497481Development of a standardized and reproducible murine femoral distraction osteogenesis modelYuejun Lin0Zhaowei Jiang1Jiaming Yang2Ming Wang3Haixing Wang4Xiaoting Zhang5Xuan Lu6Shanshan Bai7Tongzhou Liang8Botai Li9Jie Shao10Lu Zhang11Dashuang Gao12Jiajun Chen13Sien Lin14Fan Yang15Gang Li16Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, ChinaThe Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, China; University of Chinese Academy of Sciences, Beijing, ChinaThe Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, ChinaThe Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, ChinaThe Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, ChinaSchool of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, ChinaStem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Corresponding author. Room 501, 5F, LiKaShing Medical Science Building, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; The Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, Shenzhen, Guangdong, China; CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen, Guangdong, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, China; Corresponding author. 13F, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Nanshan District, Shenzhen, Guangdong, China.Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China; Corresponding author. Room 74038, 5F, Lui Chee Woo Clinical Science Building, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.Objective: Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model. Methods: A mini-titanium lengthener was designed and fabricated. The mini-lengthener was applied on the murine femur with four threaded pins using a designed clamp as the drilling and insertion guide. After transverse osteotomy using a Gigli saw, and after 5 days of latency, DO procedures started at 0.3 mm/day for 10 days, and the consolidation period was left for 28 days. The bone formation was monitored by radiography and histology. Potential effects on animal locomotion during DO were also measured by behavior tests. Results: Separated bone segments maintained good alignment during the entire DO phases. New bone formation was found as early as the end of the distraction phase. Active bone remodeling was found between the separated bone segments at late distraction and early consolidation phases. At the mature consolidation phase, bone remodeling was mainly observed in the contact cortical bone. Mice underwent DO procedure did not have significant impairment in their locomotion. Conclusion: We have successfully developed a murine femoral DO model, which may be used to study the biological processes of DO. We also developed the mini-lengthener and the guide clamp to ensure the standardization and reproducibility of the mouse DO model.The translational potential of this article: Current study reports the development of a murine femoral DO model. A well-established murine DO model will facilitate further investigations of the biological mechanisms of DO in various transgenic and normal mice.http://www.sciencedirect.com/science/article/pii/S2214031X24000871Distraction osteogenesisExternal fixatorsLimb lengtheningMouse model
spellingShingle Yuejun Lin
Zhaowei Jiang
Jiaming Yang
Ming Wang
Haixing Wang
Xiaoting Zhang
Xuan Lu
Shanshan Bai
Tongzhou Liang
Botai Li
Jie Shao
Lu Zhang
Dashuang Gao
Jiajun Chen
Sien Lin
Fan Yang
Gang Li
Development of a standardized and reproducible murine femoral distraction osteogenesis model
Journal of Orthopaedic Translation
Distraction osteogenesis
External fixators
Limb lengthening
Mouse model
title Development of a standardized and reproducible murine femoral distraction osteogenesis model
title_full Development of a standardized and reproducible murine femoral distraction osteogenesis model
title_fullStr Development of a standardized and reproducible murine femoral distraction osteogenesis model
title_full_unstemmed Development of a standardized and reproducible murine femoral distraction osteogenesis model
title_short Development of a standardized and reproducible murine femoral distraction osteogenesis model
title_sort development of a standardized and reproducible murine femoral distraction osteogenesis model
topic Distraction osteogenesis
External fixators
Limb lengthening
Mouse model
url http://www.sciencedirect.com/science/article/pii/S2214031X24000871
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