Autologous chondrocyte grafting promotes bone formation in the posterolateral spine
Background context Pseudarthrosis following spinal fusion remains problematic despite modern surgical and grafting techniques. In surgical spinal fusion, new bone forms via intramembranous and endochondral ossification, with endochondral ossification occurring in the hypoxic zones of the fusion bed....
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doaj-d976ec843257486aa5b620cf4f2a65ee2020-11-24T22:13:21ZengWileyJOR Spine2572-11432018-03-0111n/an/a10.1002/jsp2.1001Autologous chondrocyte grafting promotes bone formation in the posterolateral spineJ. Alex Sielatycki0Masanori Saito1Masato Yuasa2Stephanie N. Moore‐Lotridge3Sasidhar Uppuganti4Juan M. Colazo5Alexander A. Hysong6J. Patton Robinette7Atsushi Okawa8Toshitaka Yoshii9Herbert S. Schwartz10Jeffry S. Nyman11Jonathan G. Schoenecker12Department of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeVanderbilt University School of Medicine Nashville TennesseeVanderbilt University School of Medicine Nashville TennesseeVanderbilt University School of Medicine Nashville TennesseeDepartment of Orthopaedic Surgery Tokyo Medical and Dental University Tokyo JapanDepartment of Orthopaedic Surgery Tokyo Medical and Dental University Tokyo JapanDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeDepartment of Orthopaedics and Rehabilitation Vanderbilt University Medical Center Nashville TennesseeBackground context Pseudarthrosis following spinal fusion remains problematic despite modern surgical and grafting techniques. In surgical spinal fusion, new bone forms via intramembranous and endochondral ossification, with endochondral ossification occurring in the hypoxic zones of the fusion bed. During bone development and fracture healing, the key cellular mediator of endochondral ossification is the hypertrophic chondrocyte given its ability to function in hypoxia and induce neovascularization and ossification. We therefore hypothesize that hypertrophic chondrocytes may be an effective bone graft alternative. Purpose Spinal fusion procedures have increased substantially; yet 5% to 35% of all spinal fusions may result in pseudoarthrosis. Pseudoarthrosis may occur because of implant failure, infection, or biological failure, among other reasons. Advances in surgical techniques and bone grafting have improved fusion; however pseudarthrosis rates remain unacceptably high. Thus, the goal of this study is to investigate hypertrophic chondrocytes as a potential biological graft alternative. Methods Using a validated murine fracture model, hypertrophic chondrocytes were harvested from fracture calluses and transplanted into the posterolateral spines of identical mice. New bone formation was assessed by X‐ray, microcomputed tomography (μCT), and in vivo fluorescent imaging. Results were compared against a standard iliac crest bone graft and a sham surgery control group. Funding for this work was provided by the Department of Orthopaedics and Rehabilitation, the OREF (Grant #16‐150), and The Caitlin Lovejoy Fund. Results Radiography, μCT, and in vivo fluorescent imaging demonstrated that hypertrophic chondrocytes promoted bone formation at rates equivalent to iliac crest autograft. Additionally, μCT analysis demonstrated similar fusion rates in a subset of mice from the iliac crest and hypertrophic chondrocyte groups. Conclusions This proof‐of‐concept study indicates that hypertrophic chondrocytes can promote bone formation comparable to iliac crest bone graft. These findings provide the foundation for future studies to investigate the potential therapeutic use of hypertrophic chondrocytes in spinal fusion.https://doi.org/10.1002/jsp2.1001bone formationbone‐morphogenic proteinfracture callushypertrophic chondrocytesiliac crest bone graftossification |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
J. Alex Sielatycki Masanori Saito Masato Yuasa Stephanie N. Moore‐Lotridge Sasidhar Uppuganti Juan M. Colazo Alexander A. Hysong J. Patton Robinette Atsushi Okawa Toshitaka Yoshii Herbert S. Schwartz Jeffry S. Nyman Jonathan G. Schoenecker |
spellingShingle |
J. Alex Sielatycki Masanori Saito Masato Yuasa Stephanie N. Moore‐Lotridge Sasidhar Uppuganti Juan M. Colazo Alexander A. Hysong J. Patton Robinette Atsushi Okawa Toshitaka Yoshii Herbert S. Schwartz Jeffry S. Nyman Jonathan G. Schoenecker Autologous chondrocyte grafting promotes bone formation in the posterolateral spine JOR Spine bone formation bone‐morphogenic protein fracture callus hypertrophic chondrocytes iliac crest bone graft ossification |
author_facet |
J. Alex Sielatycki Masanori Saito Masato Yuasa Stephanie N. Moore‐Lotridge Sasidhar Uppuganti Juan M. Colazo Alexander A. Hysong J. Patton Robinette Atsushi Okawa Toshitaka Yoshii Herbert S. Schwartz Jeffry S. Nyman Jonathan G. Schoenecker |
author_sort |
J. Alex Sielatycki |
title |
Autologous chondrocyte grafting promotes bone formation in the posterolateral spine |
title_short |
Autologous chondrocyte grafting promotes bone formation in the posterolateral spine |
title_full |
Autologous chondrocyte grafting promotes bone formation in the posterolateral spine |
title_fullStr |
Autologous chondrocyte grafting promotes bone formation in the posterolateral spine |
title_full_unstemmed |
Autologous chondrocyte grafting promotes bone formation in the posterolateral spine |
title_sort |
autologous chondrocyte grafting promotes bone formation in the posterolateral spine |
publisher |
Wiley |
series |
JOR Spine |
issn |
2572-1143 |
publishDate |
2018-03-01 |
description |
Background context Pseudarthrosis following spinal fusion remains problematic despite modern surgical and grafting techniques. In surgical spinal fusion, new bone forms via intramembranous and endochondral ossification, with endochondral ossification occurring in the hypoxic zones of the fusion bed. During bone development and fracture healing, the key cellular mediator of endochondral ossification is the hypertrophic chondrocyte given its ability to function in hypoxia and induce neovascularization and ossification. We therefore hypothesize that hypertrophic chondrocytes may be an effective bone graft alternative. Purpose Spinal fusion procedures have increased substantially; yet 5% to 35% of all spinal fusions may result in pseudoarthrosis. Pseudoarthrosis may occur because of implant failure, infection, or biological failure, among other reasons. Advances in surgical techniques and bone grafting have improved fusion; however pseudarthrosis rates remain unacceptably high. Thus, the goal of this study is to investigate hypertrophic chondrocytes as a potential biological graft alternative. Methods Using a validated murine fracture model, hypertrophic chondrocytes were harvested from fracture calluses and transplanted into the posterolateral spines of identical mice. New bone formation was assessed by X‐ray, microcomputed tomography (μCT), and in vivo fluorescent imaging. Results were compared against a standard iliac crest bone graft and a sham surgery control group. Funding for this work was provided by the Department of Orthopaedics and Rehabilitation, the OREF (Grant #16‐150), and The Caitlin Lovejoy Fund. Results Radiography, μCT, and in vivo fluorescent imaging demonstrated that hypertrophic chondrocytes promoted bone formation at rates equivalent to iliac crest autograft. Additionally, μCT analysis demonstrated similar fusion rates in a subset of mice from the iliac crest and hypertrophic chondrocyte groups. Conclusions This proof‐of‐concept study indicates that hypertrophic chondrocytes can promote bone formation comparable to iliac crest bone graft. These findings provide the foundation for future studies to investigate the potential therapeutic use of hypertrophic chondrocytes in spinal fusion. |
topic |
bone formation bone‐morphogenic protein fracture callus hypertrophic chondrocytes iliac crest bone graft ossification |
url |
https://doi.org/10.1002/jsp2.1001 |
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