Abstract

Physeal injuries can lead to bony repair tissue formation, known as a bony bar. This can result in growth arrest or angular deformity, which is devastating for children who have not yet reached their full height. Current clinical treatment involves resecting the bony bar and replacing it with a fat graft to prevent further bone formation and growth disturbance, but these treatments frequently fail to do so and require additional interventions. Novel treatments that could prevent bone formation but also regenerate the injured physeal cartilage and restore normal bone elongation are warranted. To test the efficacy of these treatments, animal models that emulate human physeal injury are necessary. The rabbit model of physeal injury quickly establishes a bony bar, which can then be resected to test new treatments. Although numerous rabbit models have been reported, they vary in terms of size and location of the injury, tools used to create the injury, and methods to assess the repair tissue, making comparisons between studies difficult. The study presented here provides a detailed method to create a rabbit model of proximal tibia physeal injury using a two-stage procedure. The first procedure involves unilateral removal of 25% of the physis in a 6-week-old New Zealand white rabbit. This consistently leads to a bony bar, significant limb length discrepancy, and angular deformity within 3 weeks. The second surgical procedure involves bony bar resection and treatment. In this study, we tested the implantation of a fat graft and a photopolymerizable hydrogel as a proof of concept that injectable materials could be delivered into this type of injury. At 8 weeks post-treatment, we measured limb length, tibial angle, and performed imaging and histology of the repair tissue. By providing a detailed, easy to reproduce methodology to perform the physeal injury and test novel treatments after bony bar resection, comparisons between studies can be made and facilitate translation of promising therapies toward clinical use.

Impact Statement

This study provides details to create a rabbit model of physeal injury that can facilitate comparisons between studies and test novel regenerative medicine approaches. Furthermore, this model mimics the human, clinical situation that requires a bony bar resection followed by treatment. In addition, identification of a suitable treatment can be seen in the correction of the growth deformity, allowing this model to facilitate the development of novel physeal cartilage regenerative medicine approaches.

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Information & Authors

Information

Published In

cover image Tissue Engineering Part C: Methods
Tissue Engineering Part C: Methods
Volume 25Issue Number 12December 2019
Pages: 701 - 710
PubMed: 31552802

History

Published online: 13 December 2019
Published in print: December 2019
Published ahead of print: 31 October 2019
Published ahead of production: 25 September 2019
Accepted: 27 August 2019
Received: 15 July 2019

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Yangyi Yu
Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Francisco Rodriguez-Fontan
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Kevin Eckstein
Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado.
Archish Muralidharan
Material Science and Engineering Program, University of Colorado Boulder, Boulder, Colorado.
Asais Camila Uzcategui
Material Science and Engineering Program, University of Colorado Boulder, Boulder, Colorado.
Joseph R. Fuchs
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Shane Weatherford
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Christopher B. Erickson
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Stephanie J. Bryant
Material Science and Engineering Program, University of Colorado Boulder, Boulder, Colorado.
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado.
BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado.
Virginia L. Ferguson
Department of Mechanical Engineering, University of Colorado Boulder, Boulder, Colorado.
Material Science and Engineering Program, University of Colorado Boulder, Boulder, Colorado.
BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado.
Nancy Hadley Miller
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Guangheng Li [email protected]
Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Current address: Department of Orthopaedic Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University and The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Karin A. Payne [email protected]
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Notes

Address correspondence to: Guangheng Li, MD, Department of Orthopaedic Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University and The First Affiliated Hospital of Southern University of Science and Technology, 1017 Dongmen North Road, Shenzhen 518035, China [email protected]
Karin A. Payne, PhD, Department of Orthopedics, University of Colorado Anschutz Medical Campus, Mail Stop 8343, 12800 East 19th Avenue, Room 2102, Aurora, CO 80045 [email protected]

Disclosure Statement

No competing financial interests exist.

Funding Information

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (NIH) under award number R21HD090696 and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under award number 1R01AR069060. Research was also supported by the Gates Grubstake Fund. A Major Research Instrumentation Award from the National Science Foundation (NSF#1726864) supported the purchase of the XRM system.

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