颈椎內植物-骨界面骨整合的机制及其影响因素的研究

Clinical outcomes of the cervical total disc replacement in cervical spondylosis patients have been satisfactory, besides a relatively low incidence of implant subsidence, loose and displacement. To avoid such complications should the implant achieve the secondary stability through good bone-implant osseointegration. Among the many factors affecting the osseointegration, the loading, loading time and peri-implant gap are important yet lack of the evidence providing the exact range that could promote such process. Recent evidence has shown that osteocytes played iportant role in bone remodeling because of their mechanosensation and mechanotransduction abilities. Through the Wnt/β-catenin signaling pathway, the osteocyte could respond to the mechanical stimulation by modulating the expression of the genes of many cytokines, like TGF-β2, RANKL, OPG. Therefore, the osteocytes could interact with the osteoblasts and osteoclasts. We are going to obtain the stress of the cervical vertebral endplate at the bone-implant interface under different circumstances during the daily activity, using the finite element analysis. By using the explant vertebral bone model, we are going to simulate the various stimulations which could be encountered by postoperative patients, to explore the effects of loading and loading time on the viability and gene expression of the osteocytes. Together with the peri-implant gap model established in goat cervical spine, we hope to find the range in which the above mentioned factors could promote the bone-implant osseointegration. To know the mechanism behind the osseointegration process affected by loading and peri-implant gap is to provide the scientific basics for surgical operation and postoperative rehabilitation.

颈椎间盘置换术治疗颈椎病已取得良好的临床效果，但仍存在內植物下沉、松动、移位等问题。內植物-骨界面良好的骨整合是內植物获得长期稳定性、避免相关并发症的前提。在其诸多影响因素中，应力大小及其作用时间和內植物周围间隙在何种范围内可促进界面的骨整合尚无定论。近期研究发现骨细胞可通过其轴突感受应力刺激并经Wnt/β-catenin信号通路调控多种细胞因子的基因表达，从而调控成骨/破骨细胞的活性。本课题拟通过有限元分析得到日常生活中骨与人工颈椎间盘接触面的应力大小。然后通过建立离体骨块与內植物的体外共培养模型，模拟术后患者颈椎的多种力学环境，探究不同大小应力、不同时间加载下，骨细胞在內植物-骨界面骨整合过程中细胞的活性以及基因的表达；通过建立內植物周围间隙动物模型，探究不同大小间隙对界面骨整合的影响。以期发现上述因素能够促进內植物-骨界面骨整合的作用范围，为手术操作、患者术后康复提供理论依据。

颈椎间盘置换术治疗颈椎病已取得良好的临床效果，但仍存在內植物下沉、松动、移位等问题，这些问题不同程度的影响着患者预后，有些患者甚至需要再次手术。內植物-骨界面良好的骨整合是內植物获得长期稳定性、避免相关并发症的前提和关键，但是应力大小及其作用时间和內植物周围间隙在何种范围内可促进界面的骨整合尚无定论。研究发现骨细胞可通过其轴突感受应力刺激并经Wnt/β-cat enin信号通路调控多种细胞因子的基因表达，从而调控成骨/破骨细胞的活性。本课题成功建立颈椎有限元、山羊颈椎内植物周围间隙、新西兰兔颅骨-内植物间隙等模型，通过临床研究、动物试验、组织学和影像学等方法阐明了人工颈椎间盘-骨界面间隙对人工颈椎间盘置换术疗效的影响，不同大小界面间隙在内植物-骨界面骨整合的重要作用。同时也评估了自体骨屑在内植物-骨界面间隙模型中的成骨能力。上述重要研究进展阐述了促进内植物-骨界面骨整合的关键因素及作用范围，为手术操作、患者术后康复提供了理论依据;为基础理论转化至临床应用提供了参考。