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Published Online: 18 January 2021

Influence of Geometry and Architecture on the In Vivo Success of 3D-Printed Scaffolds for Spinal Fusion

Publication: Tissue Engineering Part A
Volume 27, Issue Number 1-2

Abstract

We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed material comprising hydroxyapatite (HA) and demineralized bone matrix (DBM) for bone regeneration. This material has demonstrated the capacity to promote re-mineralization of the DBM particles within the scaffold struts and shows potential to promote successful spine fusion. Here, we investigate the role of geometry and architecture in osteointegration, vascularization, and facilitation of spine fusion in a preclinical model. Inks containing HA and DBM particles in a poly(lactide-co-glycolide) elastomer were 3D-printed into scaffolds with varying relative strut angles (90° vs. 45° advancing angle), macropore size (0 μm vs. 500 μm vs. 1000 μm), and strut alignment (aligned vs. offset). The following configurations were compared with scaffolds containing no macropores: 90°/500 μm/aligned, 45°/500 μm/aligned, 90°/1000 μm/aligned, 45°/1000 μm/aligned, 90°/1000 μm/offset, and 45°/1000 μm/offset. Eighty-four female Sprague-Dawley rats underwent spine fusion with bilateral placement of the various scaffold configurations (n = 12/configuration). Osteointegration and vascularization were assessed by using microComputed Tomography and histology, and spine fusion was assessed via blinded manual palpation. The 45°/1000 μm scaffolds with aligned struts achieved the highest average fusion score (1.61/2) as well as the highest osteointegration score. Both the 45°/1000 μm/aligned and 90°/1000 μm/aligned scaffolds elicited fusion rates of 100%, which was significantly greater than the 45°/500 μm/aligned iteration (p < 0.05). All porous scaffolds were fully vascularized, with blood vessels present in every macropore. Vessels were also observed extending from the native transverse process bone, through the protrusions of new bone, and into the macropores of the scaffolds. When viewed independently, scaffolds printed with relative strut angles of 45° and 90° each allowed for osteointegration sufficient to stabilize the spine at L4-L5. Within those parameters, a pore size of 500 μm or greater was generally sufficient to achieve unilateral fusion. However, our results suggest that scaffolds printed with the larger pore size and with aligned struts at an advancing angle of 45° may represent the optimal configuration to maximize osteointegration and fusion capacity. Overall, this work suggests that the HA/DBM composite scaffolds provide a conducive environment for bone regeneration as well as vascular infiltration. This technology, therefore, represents a novel, growth-factor-free biomaterial with significant potential as a bone graft substitute for use in spinal surgery.

Impact statement

We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed composite material comprising hydroxyapatite and demineralized bone matrix for bone regeneration. Here, we identify a range of 3D geometric and architectural parameters that support the preclinical success of the scaffold, including efficient vascularization, osteointegration, and, ultimately, spinal fusion. Our results suggest that this material holds great promise as a clinically translatable biomaterial for use as a bone graft substitute in orthopedic procedures requiring bone regeneration.

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Information & Authors

Information

Published In

cover image Tissue Engineering Part A
Tissue Engineering Part A
Volume 27Issue Number 1-2January 2021
Pages: 26 - 36
PubMed: 32098585

History

Published online: 18 January 2021
Published in print: January 2021
Published ahead of print: 26 March 2020
Published ahead of production: 26 February 2020
Accepted: 6 February 2020
Received: 7 January 2020

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Mitchell Hallman
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
J. Adam Driscoll
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Ryan Lubbe
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Soyeon Jeong
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Kevin Chang
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Meraaj Haleem
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Adam Jakus
Simpson Querrey Institute, Chicago, Illinois, USA.
Northwestern University Department of Materials Science and Engineering, Evanston, Illinois, USA.
Transplant Division, Northwestern University Department of Surgery, Chicago, Illinois, USA.
Richard Pahapill
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Chawon Yun
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Ramille Shah
Simpson Querrey Institute, Chicago, Illinois, USA.
Northwestern University Department of Materials Science and Engineering, Evanston, Illinois, USA.
Transplant Division, Northwestern University Department of Surgery, Chicago, Illinois, USA.
Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, Michigan, USA.
Northwestern University Department of Biomedical Engineering, Evanston, Illinois, USA.
Wellington K. Hsu
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.
Stuart R. Stock
Simpson Querrey Institute, Chicago, Illinois, USA.
Argonne National Laboratory, Argonne, Illinois, USA.
Northwestern University Department of Cell and Molecular Biology, Chicago, Illinois, USA.
Erin L. Hsu [email protected]
Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.
Simpson Querrey Institute, Chicago, Illinois, USA.

Notes

Investigation performed at the Simpson Querrey Institute, Northwestern University, Chicago, Illinois, USA.
Address correspondence to: Erin L. Hsu, PhD, Northwestern University Department of Orthopaedic Surgery, 676 N. St. Clair Street, Suite 1350, Chicago, IL 60611, USA [email protected]

Disclosure Statement

M.H., A.D., R.L., K.C., M.H., R.P., S.J., C.Y., W.H., S.R.S., and E.H. have no commercial associations that might create a conflict of interest in connection with this work. A.J. and R.S. are co-founders of and shareholders in Dimension Inx, LLC, which develops and manufactures new advanced manufacturing compatible materials and devices for medical and nonmedical applications, including some of the materials on which this work is based (i.e., Hyperelastic Bone). As of August 2017, A.J. is currently full-time Chief Technology Officer of Dimension Inx, LLC, and R.S. serves part time as Chief Science Officer of Dimension Inx LLC. A.J. and R.S. are inventors on relevant patents that are licensed to Dimension Inx LLC. Dimension Inx owns the trademark for Hyperelastic Bone. Dimension Inx LLC did not influence the conduct, description, or interpretation of the findings in this article. No other authors have commercial interests in the materials described in this work.

Funding Information

This study was supported by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases, grant R01AR069580. This research used resources of the Northwestern University Center for Advanced Microscopy Core Facility (National Cancer Institute Cancer Center Support Grant P30 CA060553 to the Robert H. Lurie Comprehensive Cancer Center); Histology and Phenotyping Core Facility (Robert H. Lurie Comprehensive Cancer Center support grant NCI CA060553); and the Rush University MicroCT and Histology Core Facility. Portions of this work were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, The Dow Chemical Company, and DuPont de Nemours, Inc. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.

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