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

Mitchell Hallman, J. Adam Driscoll, Ryan Lubbe, Soyeon Jeong, Kevin Chang, Meraaj Haleem, Adam Jakus, Richard Pahapill, Chawon Yun, Ramille Shah, Wellington K. Hsu, Stuart R. Stock, Erin L. Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)26-36
Number of pages11
JournalTissue Engineering - Part A
Volume27
Issue number1-2
DOIs
StatePublished - Jan 1 2021

Funding

This study was supported by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases, grant R01A R069580. This research used resources of the North-western 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.

Keywords

  • 3D printing
  • bone regeneration
  • ceramic scaffold
  • demineralized bone matrix
  • spine fusion

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

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