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| ZHU Xi,LI Yu,SHI Jiandang.Study on osteogenic properties and sustained release of 3D printed PaMZ/BMP-2-loaded nHA artificial bone in vivo[J].Chinese Journal of Spine and Spinal Cord,2023,(11):1032-1042. |
| Study on osteogenic properties and sustained release of 3D printed PaMZ/BMP-2-loaded nHA artificial bone in vivo |
| Received:April 01, 2022 Revised:September 17, 2023 |
| English Keywords:Spinal tuberculosis 3D printing Artificial bone PaMZ Sustained release in vivo |
| Fund:国家自然科学基金项目（编号：81760399，82060402） |
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| English Abstract: |
| 【Abstract】 Objectives: To observe the osteogenic properties and sustained release of 3D printed nano-hydroxyapatite(nHA) artificial bone loaded with a novel triple anti-tuberculosis drug combination(PaMZ) of Pretomanid(Pa), Moxifloxacin(M), Pyrazinamide(Z) and bone morphogenetic protein 2(BMP-2) in vivo. Methods: 40 New Zealand rabbits were divided into four groups randomly and constructed spinal bone defect models. Group A(experimental group) implanted with 3D-printed PaMZ/BMP-2-loaded nHA artificial bone; group B(negative control group) implanted with blank nHA artificial bone; group C(positive control group) implanted with autologous iliac bone; group D(blank group) without bone grafting. The general conditions were observed, body temperature, weight, and liver and kidney function were monitored. The bone defect restoration was observed by spiral CT 3D reconstruction at the 4th, 8th and 12th week postoperatively and was evaluated with CT-Hedberg scale; the gross observation of tissues and histopathological observation of the implants-bone defect interface were carried out at the 8th and 12th week postoperatively. 100 SD rats were divided into two groups randomly, experimental group implanted with 3D-printed PaMZ/BMP-2-loaded nHA artificial bone, control group implanted with blank nHA artificial bone. The drug concentrations in the plasma and muscle tissue around the material at different time points was tested with high performance liquid chromatography. Results: All animal models were successfully constructed without incision infection or death. The body temperature, weight and liver and kidney function indexes of the experimental groups in the rabbit models were normal, with no statistical differences from those of the control groups(P>0.05). The CT-Hedberg score showed that there was no statistical difference between group A and group C at the 4th, 8th and 12th week(P>0.05), however, there was statistical difference between all the other groups at different time points(P<0.05). The observation of the gross specimens at the 12th week after surgery showed that the artificial bone in group A was completely encapsulated or replaced by new bone, but there was still some artificial bone exposed in group B. Quantitative analysis of the total trabecular area at the implant-bone defect interface showed no statistical difference between groups A and C at the 8th and 12th week postoperatively(P>0.05), and a statistical difference between the remaining groups(P<0.05). No drug components were detected in the SD rat model control group, the three drugs Pa, M, Z in experimental group can be sustained-released in local tissues for at least 84d. The blood drug concentration was not detected at the initial time point after local implantation of the drug-loaded artificial bone, and the subsequent measured results were much lower than the local tissue drug concentration, and the two had a positive correlation. Conclusions: The 3D printed PaMZ/BMP-2-loaded nHA artificial bone has good osteogenic properties in vivo, the effect of restoring spinal bone defects is comparable to that of autologous iliac bone, which is better than that of HA artificial bone scaffold alone. Its sustained release behavior in vivo is satisfactory, and the blood drug concentration is much lower than the local tissue drug concentration. |
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