小尾寒羊颈椎前路椎间盘切除融合模型 的建立及评估
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1. 北京大学第三医院骨科,北京 100191;2. 教育部骨与关节精准医学工程研究中心,北京 100191; 3. 脊柱疾病研究北京市重点实验室,北京 100191;4. 首都医科大学附属北京友谊医院骨科, 北京 100050;5. 山东第一医科大学附属省立医院脊柱外科,济南 250000;6. 中奥汇成 科技股份有限公司,北京 100176;7. 北京大学第三医院实验动物中心,北京 100191

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Establishment and evaluation of anterior cervical discectomy fusion model in small⁃tailed Han sheep model
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1.Department of Orthopaedics, Peking University Third Hospital, Beijing 100191, China; 2. Engineering Research Center of Bone and Joint Precision Medicine, Ministry of Education, Beijing 100191, China; 3. Beijing Key Laboratory of Spinal Disease Research, Beijing 100191, China; 4. Department of Orthopaedics, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, China; 5. Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, China; 6. Zhongaohuicheng Technology Co. , Beijing 100176, China; 7. Laboratory Animal Research Center, Peking University Third Hospital, Beijing 100191, China

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    摘要:

    目的 颈椎间盘突出症(cervical disc herniation,CDH)是骨科常见疾病之一,随着对该疾病研究的深入及颈椎内植物的发展,建立颈椎融合动物模型成为不可或缺的部分,目前国内对颈椎融合动物模型建立及评估的研究报道较少,本研究以期为颈椎融合相关研究提供完备的动物模型和内植物性能的评估方案。 方法 选择小尾寒羊,改良术式后行颈椎前路椎间盘切除融合术( anterior cervical discectomy and fusion,ACDF),将聚醚醚酮(polyetheretherketone,PEEK)椎间融合器(interbody fusion cage,Cage)(对照组)、3D 打印钛合金 Cage(实验组 1)及新方法钛合金 Cage(实验组 2)分别植入每只羊的不同颈椎节段(C2 / 3 ~ C4 / 5),术后行血液学检测、组织病理学分析评估手术恢复情况及材料生物安全性,利用 X 光、CT、Micro-CT 及定量分析、硬组织切片染色、生物力学试验评估内植物的骨长入及骨融合情况。 结果 绵羊改良术式 ACDF 模型建立成功,血液学检测重要指标无显著性差异(P> 0. 05), 组织病理学分析显示均无炎症细胞浸润等病理改变,内植物生物安全性良好,X 光及 CT 显示内固定位置及椎间融合情况良好,术后 3 个月及 6 个月 Micro-CT 及定量分析表明,与 PEEK Cage 组相比,新方法钛合金Cage 组及 3D 打印钛合金 Cage 组内部的骨体积/ 总体积、骨小梁数目显著性升高(P< 0. 01),骨小梁间距显著性降低(P< 0. 01), 且新方法钛合金 Cage 组骨质长入更多(P< 0. 01),硬组织切片染色表明新方法钛合金 Cage 组及3D 打印钛合金 Cage 组孔隙内有明显骨质长入且较为密实,结合较 PEEK Cage 组略好,生物力学试验显示,与PEEK Cage 组相比,新方法钛合金 Cage 及 3D 打印钛合金 Cage 在一定程度上降低了颈椎屈伸、侧弯、扭转运动范围(P< 0. 05), 同时增强了颈椎的稳定性,且新方法钛合金 Cage 更有优势(P< 0. 05)。 结论 建立绵羊改良术式ACDF 模型后,利用合理有效的评估方法,证明了该模型的合理性及有效性,同时说明 3 种材料的 Cage 均显示出良好的生物安全性,新方法钛合金 Cage 及 3D 打印钛合金 Cage 较 PEEK Cage 的骨长入及骨融合性能更强,可增强颈椎的稳定性,且新方法钛合金 Cage 更有优势。

    Abstract:

    Objective Cervical disc herniation (CDH) is one of the common orthopaedic diseases. With the indepth study of it and the development of cervical implants, the establishment of cervical fusion animal models has become an indispensable part. Notably however, studies of the establishment and evaluation of cervical fusion animal models in China are currently lacking. This study aimed to provide a suitable animal model and evaluation scheme for implants for cervical spine-related research. Methods Small-tailed Han sheep were chosen for anterior cervical discectomy fusion(ACDF) after modified surgery, and a polyetheretherketone (PEEK) interbody fusion cage (Cage) (control group), 3Dprinted Ti6Al4V Cage (group 1), and new method Ti6Al4V Cage (group 2) were implanted in different cervical segments(C2 / 3 ~ C4 / 5) in each sheep, respectively. Hematology and histopathological analyses were carried out after surgery to evaluate recovery of sheep and the biosafety of the materials. Bone in-growth and bone fusion were assessed by X-ray,computed tomography (CT), Micro-CT and quantitative analysis, hard tissue section staining, and biomechanical tests. Results The modified ACDF ovine model was established successfully. There were no significant differences in important hematology indexes (P> 0. 05) and histopathological analysis showed no pathological changes, such as inflammatory cell infiltration. The implants had good biosafety. Furthermore, X-ray and CT examinations showed that the position of internal fixation and the interbody fusion were good. Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group, the bone volume / total volume and trabecular number were significantly increased (P< 0. 01) while the trabecular spacing was significantly decreased in the new method Ti6Al4V and 3D-printed Ti6Al4V groups compared with the PEEK Cage group (P< 0. 01). Moreover, the new method new method Ti6Al4V Cage group had more bone growth (P< 0. 01). Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and relatively dense pores in the new method Ti6Al4V and 3Dprinted Ti6Al4V groups, and the combination was slightly better than that of PEEK Cage. Biomechanical evaluation indicated that the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extension,lateral bending, and axial rotation (P< 0. 05) compared with the PEEK cage, as well as enhancing the stability of the cervical vertebra, and the new method Ti6Al4V Cage was more advantageous ( P< 0. 05). Conclusions After the establishment of the modified ACDF ovine model, reasonable and effective assessment method were used to demonstrate the suitability and effectiveness of the model and the good biosecurity of all three Cage materials. Compared with the PEEK Cage, the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cages showed better performances in terms of bone growth and bone fusion, which could enhance the stability of the cervical vertebrae. The new method Ti6Al4V Cage was particularly advantageous.

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窦新雨,刘宇,刘啸,祝斌,贾斐,王霖邦,金攻,沈飞,刘晓光.小尾寒羊颈椎前路椎间盘切除融合模型 的建立及评估[J].中国实验动物学报,2024,32(02):138~150.

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  • 收稿日期:2023-08-04
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  • 在线发布日期: 2024-05-14
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