A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model

Abstract Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No tr...

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Main Authors: Yangyi Yu, Kristine M. Fischenich, Sarah A. Schoonraad, Shane Weatherford, Asais Camila Uzcategui, Kevin Eckstein, Archish Muralidharan, Victor Crespo-Cuevas, Francisco Rodriguez-Fontan, Jason P. Killgore, Guangheng Li, Robert R. McLeod, Nancy Hadley Miller, Virginia L. Ferguson, Stephanie J. Bryant, Karin A. Payne
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-022-00256-1
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author Yangyi Yu
Kristine M. Fischenich
Sarah A. Schoonraad
Shane Weatherford
Asais Camila Uzcategui
Kevin Eckstein
Archish Muralidharan
Victor Crespo-Cuevas
Francisco Rodriguez-Fontan
Jason P. Killgore
Guangheng Li
Robert R. McLeod
Nancy Hadley Miller
Virginia L. Ferguson
Stephanie J. Bryant
Karin A. Payne
author_facet Yangyi Yu
Kristine M. Fischenich
Sarah A. Schoonraad
Shane Weatherford
Asais Camila Uzcategui
Kevin Eckstein
Archish Muralidharan
Victor Crespo-Cuevas
Francisco Rodriguez-Fontan
Jason P. Killgore
Guangheng Li
Robert R. McLeod
Nancy Hadley Miller
Virginia L. Ferguson
Stephanie J. Bryant
Karin A. Payne
author_sort Yangyi Yu
collection DOAJ
description Abstract Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No treatment attempts to regenerate the growth plate cartilage. Herein we develop a 3D printed growth plate mimetic composite as a potential regenerative medicine approach with the goal of preventing limb length discrepancies and inducing cartilage regeneration. A poly(ethylene glycol)-based resin was used with digital light processing to 3D print a mechanical support structure infilled with a soft cartilage-mimetic hydrogel containing chondrogenic cues. Our biomimetic composite has similar mechanical properties to native rabbit growth plate and induced chondrogenic differentiation of rabbit mesenchymal stromal cells in vitro. We evaluated its efficacy as a regenerative interpositional material applied after bony bar resection in a rabbit model of growth plate injury. Radiographic imaging was used to monitor limb length and tibial plateau angle, microcomputed tomography assessed bone morphology, and histology characterized the repair tissue that formed. Our 3D printed growth plate mimetic composite resulted in improved tibial lengthening compared to an untreated control, cartilage-mimetic hydrogel only condition, and a fat graft. However, in vivo the 3D printed growth plate mimetic composite did not show cartilage regeneration within the construct histologically. Nevertheless, this study demonstrates the feasibility of a 3D printed biomimetic composite to improve limb lengthening, a key functional outcome, supporting its further investigation as a treatment for growth plate injuries.
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spelling doaj.art-cee248cd0eb9411787229f61ddd067102022-12-22T03:26:20ZengNature Portfolionpj Regenerative Medicine2057-39952022-10-017111410.1038/s41536-022-00256-1A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit modelYangyi Yu0Kristine M. Fischenich1Sarah A. Schoonraad2Shane Weatherford3Asais Camila Uzcategui4Kevin Eckstein5Archish Muralidharan6Victor Crespo-Cuevas7Francisco Rodriguez-Fontan8Jason P. Killgore9Guangheng Li10Robert R. McLeod11Nancy Hadley Miller12Virginia L. Ferguson13Stephanie J. Bryant14Karin A. Payne15Colorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical CampusColorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical CampusMaterials Science and Engineering Program, University of Colorado BoulderColorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical CampusMaterials Science and Engineering Program, University of Colorado BoulderDepartment of Mechanical Engineering, University of Colorado BoulderMaterials Science and Engineering Program, University of Colorado BoulderDepartment of Mechanical Engineering, University of Colorado BoulderColorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical CampusApplied Chemicals and Materials Division (647), National Institute of Standards and Technology (NIST)Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Department of Bone and Joint Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Materials Science and Engineering Program, University of Colorado BoulderColorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical CampusDepartment of Mechanical Engineering, University of Colorado BoulderMaterials Science and Engineering Program, University of Colorado BoulderColorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado Anschutz Medical CampusAbstract Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No treatment attempts to regenerate the growth plate cartilage. Herein we develop a 3D printed growth plate mimetic composite as a potential regenerative medicine approach with the goal of preventing limb length discrepancies and inducing cartilage regeneration. A poly(ethylene glycol)-based resin was used with digital light processing to 3D print a mechanical support structure infilled with a soft cartilage-mimetic hydrogel containing chondrogenic cues. Our biomimetic composite has similar mechanical properties to native rabbit growth plate and induced chondrogenic differentiation of rabbit mesenchymal stromal cells in vitro. We evaluated its efficacy as a regenerative interpositional material applied after bony bar resection in a rabbit model of growth plate injury. Radiographic imaging was used to monitor limb length and tibial plateau angle, microcomputed tomography assessed bone morphology, and histology characterized the repair tissue that formed. Our 3D printed growth plate mimetic composite resulted in improved tibial lengthening compared to an untreated control, cartilage-mimetic hydrogel only condition, and a fat graft. However, in vivo the 3D printed growth plate mimetic composite did not show cartilage regeneration within the construct histologically. Nevertheless, this study demonstrates the feasibility of a 3D printed biomimetic composite to improve limb lengthening, a key functional outcome, supporting its further investigation as a treatment for growth plate injuries.https://doi.org/10.1038/s41536-022-00256-1
spellingShingle Yangyi Yu
Kristine M. Fischenich
Sarah A. Schoonraad
Shane Weatherford
Asais Camila Uzcategui
Kevin Eckstein
Archish Muralidharan
Victor Crespo-Cuevas
Francisco Rodriguez-Fontan
Jason P. Killgore
Guangheng Li
Robert R. McLeod
Nancy Hadley Miller
Virginia L. Ferguson
Stephanie J. Bryant
Karin A. Payne
A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model
npj Regenerative Medicine
title A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model
title_full A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model
title_fullStr A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model
title_full_unstemmed A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model
title_short A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model
title_sort 3d printed mimetic composite for the treatment of growth plate injuries in a rabbit model
url https://doi.org/10.1038/s41536-022-00256-1
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