3D-Printed Ceramic-Demineralized Bone Matrix Hyperelastic Bone Composite Scaffolds for Spinal Fusion

J. Adam Driscoll, Ryan Lubbe, Adam E. Jakus, Kevin Chang, Meraaj Haleem, Chawon Yun, Gurmit Singh, Andrew D. Schneider, Karina M. Katchko, Carmen Soriano, Michael Newton, Tristan Maerz, Xin Li, Kevin Baker, Wellington K. Hsu, Ramille N. Shah, Stuart R. Stock, Erin L. Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Although numerous spinal biologics are commercially available, a cost-effective and safe bone graft substitute material for spine fusion has yet to be proven. In this study, "3D-Paints" containing varying volumetric ratios of hydroxyapatite (HA) and human demineralized bone matrix (DBM) in a poly(lactide-co-glycolide) elastomer were three-dimensional (3D) printed into scaffolds to promote osteointegration in rats, with an end goal of spine fusion without the need for recombinant growth factor. Spine fusion was evaluated by manual palpation, and osteointegration and de novo bone formation within scaffold struts were evaluated by laboratory and synchrotron microcomputed tomography and histology. The 3:1 HA:DBM composite achieved the highest mean fusion score and fusion rate (92%), which was significantly greater than the 3D printed DBM-only scaffold (42%). New bone was identified extending from the host transverse processes into the scaffold macropores, and osteointegration scores correlated with successful fusion. Strikingly, the combination of HA and DBM resulted in the growth of bone-like spicules within the DBM particles inside scaffold struts. These spicules were not observed in DBM-only scaffolds, suggesting that de novo spicule formation requires both HA and DBM. Collectively, our work suggests that this recombinant growth factor-free composite shows promise to overcome the limitations of currently used bone graft substitutes for spine fusion. Currently, there exists a no safe, yet highly effective, bone graft substitute that is well accepted for use in spine fusion procedures. With this work, we show that a three-dimensional printed scaffold containing osteoconductive hydroxyapatite and osteoinductive demineralized bone matrix that promotes new bone spicule formation, osteointegration, and successful fusion (stabilization) when implemented in a preclinical model of spine fusion. Our study suggests that this material shows promise as a recombinant growth factor-free bone graft substitute that could safely promote high rates of successful fusion and improve patient care.

Original languageEnglish (US)
Pages (from-to)157-166
Number of pages10
JournalTissue Engineering - Part A
Volume26
Issue number3-4
DOIs
StatePublished - Feb 2020

Funding

This study was supported by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases, grant R01AR069580. A pilot grant from the Northwestern University Clinical and Translational Sciences (NUCATS) program also supported part of this work. We thank Danielle Chun, Joseph Weiner, Michael Schallmo, Ralph Cook, and John Yun for contributing as surgeons. This research used resources of the APS, a U.S. DOE Office of Science User Facility operated by Argonne National Laboratory under Contract No. DE-AC02-06CH11357; North-western’s EPIC facility, NUANCE Center supported by the Soft and Hybrid Nanotechnology Experimental Resource (NSF ECCS-1542205), the MRSEC program (NSF DMR-1720139) at the Materials Research Center, the International Institute for Nanotechnology (IIN), the Keck Foundation and the State of Illinois, through the IIN; Northwestern’s Center for Advanced Microscopy (National Cancer Institute Cancer Center Support Grant P30 CA060553 to the Robert H. Lurie Comprehensive Cancer Center); and Northwestern’s Histology and Phenotyping Laboratory (Robert H. Lurie Comprehensive Cancer Center support grant NCI CA060553). A.J. was partially supported through a postdoctoral fellowship by The Hartwell Foundation.

Keywords

  • 3D printing
  • demineralized bone matrix
  • hydroxyapatite
  • osteointegration
  • spine fusion

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

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