| Autor: |
Hallman M; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Driscoll JA; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Lubbe R; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Jeong S; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Chang K; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Haleem M; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Jakus A; 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., Pahapill R; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Yun C; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Shah R; 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., Hsu WK; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA., Stock SR; Simpson Querrey Institute, Chicago, Illinois, USA.; Argonne National Laboratory, Argonne, Illinois, USA.; Northwestern University Department of Cell and Molecular Biology, Chicago, Illinois, USA., Hsu EL; Northwestern University Department of Orthopaedic Surgery, Chicago, Illinois, USA.; Simpson Querrey Institute, Chicago, Illinois, USA. |
| Abstrakt: |
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. |
