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

Although many spinal biologic products are available, a cost-effective and universally safe bone graft substitute material for spine fusion has yet to be proven. Additive manufacturing has enhanced our ability to utilize different biomaterials to engineer structurally stable bone grafts. Here, components with both osteoinductive and osteoconductive properties (synthetic hydroxyapatite (HA) and demineralized bone matrix (DBM) particles in a poly(lactide-co-glycolide), PLG, elastomer) were 3D-printed into a scaffold to promote osteointegration with an end goal of spine fusion without the need for recombinant growth factor. "3D-Paints" containing a minority component of PLG and varying volumetric ratios of synthetic HA and human DBM particles (1:0, 3:1, 1:1, 1:3, and 0:1 HA:DBM) were printed into scaffolds for bilateral implantation at the L4-L5 transverse processes in female Sprague-Dawley rats (N=12/group). Manual palpation was used to evaluate spine fusion 8 weeks post-operatively. Osteointegration and de novo bone formation within struts were evaluated by laboratory and synchrotron microCT and histology. The 3:1 HA:DBM composite achieved both 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 transverse processes into adjacent scaffold macropores, and osteointegration scores (extent of bone growth into scaffolds) correlated with fusion scores. Strikingly, synchrotron microCT imaging showed that the combination of HA and DBM resulted in the growth of bone-like spicules around the DBM particles inside scaffold struts. These mineralized spicules were not observed in DBM-only scaffolds, suggesting that de novo spicule formation requires both the HA and DBM components. This 3D-printable composite scaffold exploits the advantages of additive manufacturing and the combined properties of HA and DBM to promote de novo bone formation and stabilize the spine in a rat model. Thus, this recombinant growth factor-free material may have the potential to overcome the limitations of currently-used bone graft substitutes for spinal fusion.