Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion

Mark Plantz; Joseph Lyons; Jonathan T. Yamaguchi; Allison C. Greene; David J. Ellenbogen; Mitchell J. Hallman; Vivek Shah; Chawon Yun; Adam E. Jakus; Daniele Procissi; Silvia Minardi; Ramille N. Shah; Wellington K. Hsu; Erin L. Hsu

doi:10.1097/BRS.0000000000004142

Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion

Mark Plantz, Joseph Lyons, Jonathan T. Yamaguchi, Allison C. Greene, David J. Ellenbogen, Mitchell J. Hallman, Vivek Shah, Chawon Yun, Adam E. Jakus, Daniele Procissi, Silvia Minardi, Ramille N. Shah, Wellington K. Hsu, Erin L. Hsu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Study Design.Prospective, randomized, controlled preclinical study.Objective.The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model.Summary of Background Data.Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed.Methods.Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 μg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n = 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N = 5/time point).Results.At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-α and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals.Conclusion.The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.Level of Evidence: N/A.

Original language	English (US)
Pages (from-to)	82-89
Number of pages	8
Journal	Spine
Volume	47
Issue number	1
DOIs	https://doi.org/10.1097/BRS.0000000000004142
State	Published - Jan 1 2022

Funding

This project was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR069580-04). Imaging work was performed at the Northwestern University Center for Advanced Microscopy, which is supported by NCI CCSG P30 CA060553, awarded to the Robert H Lurie Comprehensive Cancer Center. A portion of the biochemical analysis was performed using instruments in the Analytical bioNanoTech-nology Core Facility of the Simpson Querrey Institute at Northwestern University. ANTEC is currently supported by the Soft and Hybrid Nano-technology Experimental (SHyNE) Resource (NSF ECCS-2025633).

Keywords

3D printing
bone morphogenetic protein-2
demineralized bone matrix
host inflammatory response
hydroxyapatite
spinal fusion

ASJC Scopus subject areas

Clinical Neurology
Orthopedics and Sports Medicine

Access to Document

10.1097/BRS.0000000000004142

Cite this

@article{a2154cf90b2c420f8cba9b11eedbe10d,

title = "Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion",

abstract = "Study Design.Prospective, randomized, controlled preclinical study.Objective.The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model.Summary of Background Data.Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed.Methods.Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 μg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n = 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N = 5/time point).Results.At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-α and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals.Conclusion.The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.Level of Evidence: N/A.",

keywords = "3D printing, bone morphogenetic protein-2, demineralized bone matrix, host inflammatory response, hydroxyapatite, spinal fusion",

author = "Mark Plantz and Joseph Lyons and Yamaguchi, \{Jonathan T.\} and Greene, \{Allison C.\} and Ellenbogen, \{David J.\} and Hallman, \{Mitchell J.\} and Vivek Shah and Chawon Yun and Jakus, \{Adam E.\} and Daniele Procissi and Silvia Minardi and Shah, \{Ramille N.\} and Hsu, \{Wellington K.\} and Hsu, \{Erin L.\}",

note = "Funding Information: This project was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR069580-04). Imaging work was performed at the Northwestern University Center for Advanced Microscopy, which is supported by NCI CCSG P30 CA060553, awarded to the Robert H Lurie Comprehensive Cancer Center. A portion of the biochemical analysis was performed using instruments in the Analytical bioNanoTech-nology Core Facility of the Simpson Querrey Institute at Northwestern University. ANTEC is currently supported by the Soft and Hybrid Nano-technology Experimental (SHyNE) Resource (NSF ECCS-2025633). Publisher Copyright: {\textcopyright} 2022 Lippincott Williams and Wilkins. All rights reserved.",

year = "2022",

month = jan,

day = "1",

doi = "10.1097/BRS.0000000000004142",

language = "English (US)",

volume = "47",

pages = "82--89",

journal = "Spine",

issn = "0362-2436",

publisher = "Wolters Kluwer Health",

number = "1",

}

TY - JOUR

T1 - Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion

AU - Plantz, Mark

AU - Lyons, Joseph

AU - Yamaguchi, Jonathan T.

AU - Greene, Allison C.

AU - Ellenbogen, David J.

AU - Hallman, Mitchell J.

AU - Shah, Vivek

AU - Yun, Chawon

AU - Jakus, Adam E.

AU - Procissi, Daniele

AU - Minardi, Silvia

AU - Shah, Ramille N.

AU - Hsu, Wellington K.

AU - Hsu, Erin L.

N1 - Funding Information: This project was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR069580-04). Imaging work was performed at the Northwestern University Center for Advanced Microscopy, which is supported by NCI CCSG P30 CA060553, awarded to the Robert H Lurie Comprehensive Cancer Center. A portion of the biochemical analysis was performed using instruments in the Analytical bioNanoTech-nology Core Facility of the Simpson Querrey Institute at Northwestern University. ANTEC is currently supported by the Soft and Hybrid Nano-technology Experimental (SHyNE) Resource (NSF ECCS-2025633). Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Study Design.Prospective, randomized, controlled preclinical study.Objective.The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model.Summary of Background Data.Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed.Methods.Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 μg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n = 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N = 5/time point).Results.At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-α and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals.Conclusion.The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.Level of Evidence: N/A.

AB - Study Design.Prospective, randomized, controlled preclinical study.Objective.The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model.Summary of Background Data.Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed.Methods.Sixty female Sprague-Dawley rats underwent bilateral posterolateral intertransverse lumbar spinal fusion using with the following implants: 1) type I absorbable collagen sponge (ACS) alone; 2) 10 μg rhBMP-2/ACS; or 3) the 3DP HA-DBM composite scaffold (n = 20). The host inflammatory response was assessed using magnetic resonance imaging, while the local and circulating cytokine expression levels were evaluated by enzyme-linked immunosorbent assays at subsequent postoperative time points (N = 5/time point).Results.At both 2 and 5 days postoperatively, treatment with the HA-DBM scaffold produced significantly less soft tissue edema at the fusion bed site relative to rhBMP-2-treated animals as quantified on magnetic resonance imaging. At every postoperative time point evaluated, the level of soft tissue edema in HA-DBM-treated animals was comparable to that of the ACS control group. At 2 days postoperatively, serum concentrations of tumor necrosis factor-α and macrophage chemoattractant protein-1 were significantly elevated in the rhBMP-2 treatment group relative to ACS controls, whereas these cytokines were not elevated in the HA-DBM-treated animals.Conclusion.The 3D-printed HA-DBM composite induces a significantly reduced host inflammatory response in a preclinical spinal fusion model relative to rhBMP-2.Level of Evidence: N/A.

KW - 3D printing

KW - bone morphogenetic protein-2

KW - demineralized bone matrix

KW - host inflammatory response

KW - hydroxyapatite

KW - spinal fusion

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JF - Spine

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Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion

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