Systematic Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Apr 18, 2019; 10(4): 176-191
Published online Apr 18, 2019. doi: 10.5312/wjo.v10.i4.176
Investigational growth factors utilized in animal models of spinal fusion: Systematic review
Ethan Cottrill, A Karim Ahmed, Noah Lessing, Zachary Pennington, Wataru Ishida, Alexander Perdomo-Pantoja, Sheng-fu Lo, Elizabeth Howell, Christina Holmes, C Rory Goodwin, Nicholas Theodore, Daniel M Sciubba, Timothy F Witham
Ethan Cottrill, A Karim Ahmed, Noah Lessing, Zachary Pennington, Wataru Ishida, Alexander Perdomo-Pantoja, Sheng-fu Lo, Christina Holmes, Nicholas Theodore, Daniel M Sciubba, Timothy F Witham, Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore, MD 21287, United States
Elizabeth Howell, C Rory Goodwin, Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, United States
Author contributions: Cottrill E, Ahmed AK, Lessing N, Pennington Z, Howell E: Conception and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for intellectual content. Ishida W, Perdomo-Pantoja A, Lo SF, Holmes C, Goodwin CR, Theodore N, Sciubba DM: Conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, supervision. Witham TF: Conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, obtaining funding, supervision. All authors reviewed and approved the final manuscript as submitted.
Conflict-of-interest statement: Goodwin CR: Grants from NIH/NINDS K12 Physician Scientist Award, North Carolina Spine Society, and Burroughs Wellcome Funds; all outside the submitted work. Lo SF: Research support from Chordoma Foundation, Grant from AO Spine; all outside the submitted work. Sciubba DM: Consulting from Baxter, DePuy Synthes, Globus, K2M, Medical Device Business Services, Medtronic, NuVasive, and Stryker; Speaking/Teaching from Globus Medical, Medtronic, and DePuy Synthes; all outside the submitted work. Theodore N: Royalties from Globus Medical, Depuy Synthes; Stock in Globus Medical; Consulting from Globus Medical; Scientific Advisory Board from Globus Medical; Fellowship Support from AO North America; all outside the submitted work. Witham TF: Grants from Eli Lilly Company and the Gordon and Marilyn Macklin Foundation.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ethan Cottrill, MSc, Research Scientist, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, United States. ecottri1@jhmi.edu
Telephone: +1-410-9554424
Received: October 22, 2018
Peer-review started: October 23, 2018
First decision: November 15, 2018
Revised: January 3, 2019
Accepted: January 26, 2019
Article in press: January 26, 2019
Published online: April 18, 2019
Core Tip

Core tip: This is the first study to systematically review all the published investigational growth factors utilized in preclinical animal models of spinal fusion. Among the identified growth factors, calcitonin, GDF-5, NELL-1, and P-15 resulted in fusion rates of 100% in some studies. In addition, six growth factors - AB204, angiopoietin 1, GDF-5, insulin, NELL-1, and peptide B2A - resulted in significantly enhanced fusion rates compared to autologous iliac crest bone graft, BMP-2, or other internal controls in some cases. Directly comparing the fusion efficacy and safety of these growth factors may inform the development of clinically translatable materials for spinal fusion.