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种植体表面不同形貌对骨质疏松症骨结合的影响

Effect of Hierarchical Micro/nano Surface Titanium Implant on Osseointegration in Ovariectomized Sheep

【作者】 周弘

【导师】 刘宝林; 孔亮;

【作者基本信息】 第四军医大学 , 颌面外科, 2011, 博士

【摘要】 实验一去势后绵羊不同部位骨质变化及颌骨骨质疏松动物模型的建立目的探索绵羊去势后建立颌骨骨质疏松模型的时间,比较去势后颌骨与其它部位骨骼变化的差异,检测骨质疏松颌骨的皮质骨、松质骨的微观结构特点及其生物力学性能,建立适用于颌骨骨质疏松相关研究的绝经后骨质疏松大动物模型。方法12只成年绵羊随机分为2组,去势组7只,假手术组5只。去势组绵羊切除双侧卵巢,同时辅以甲泼尼龙琥珀酸钠(0.45mg/kg.d)和低钙饮食。术后6个月、12个月时检测腰椎和下颌骨的BMD的变化。所有动物与去势术后12个月时处死,应用MicroCT、组织形态观察和生物力学的方法,检测颌骨骨质疏松时皮质骨结构和厚度、骨小梁三维微观结构和生物力学的变化,同时与股骨、腰椎、肋骨进行比较。结果去势12个月后,绵羊下颌骨的BMD值下降了31.0% (P <0.05);下颌皮质骨厚度及松质骨BV/TV、Tb.Th、Tb.N均显著低于对照组(P <0.05), Tb.Sp和TBPf显著高于对照组(P <0.05);下颌骨的轴向最大压缩应力降低34.2%(P <0.05);组织形态学观察可见骨小梁稀疏、变细甚至中断,失去正常拱桥状结构。结论①通过去势、糖皮质激素加低钙饮食的方法可以建立绵羊颌骨骨质疏松模型,采用此方法建模需要1年左右时间。②绵羊去势后时颌骨骨丧失晚于腰椎,但也可发生骨质疏松。实验二纯钛种植体微/纳米表面对正常骨质骨结合的影响目的比较机械加工表面、微米结构表面及微/纳米复合结构表面三种类型的种植体对骨结合和生物力学性能的影响。方法机械加工的纯钛种植体依次通过氢氟酸酸蚀、阳极氧化的处理,形成机械加工表面、微米机构表面及微/纳米复合结构表面三种类型的种植体。在8只绵羊的双侧下颌骨各植入三种类型的种植体,3个月后通过共振频率检测、MicroCT、组织形态计量学观察及生物力学的方法,检测三种表面形貌对种植体骨结合和稳定性的影响。结果种植体植入三个月后,微/纳米表面组ISQ较机械加工组、微米表面组分别提高15.47%、11.50%(P <0.05),微/纳米表面组BIC较机械加工表面组、微米表面组分别提高34.07%、23.15%(P <0.05),微/纳米表面组最大拔出力较机械加工表面组、微米表面组分别提高24.35%、11.77%(P <0.05),微/纳米表面组BV/TV、Tb.Sp、TBPf与机械加工组、微米表面组比较差异均有显著性(P <0.05)。结论①在正常骨质情况下,种植体表面的微/纳米复合结构可以有效的提高种植体的骨结合率,增加种植体的稳定性,但对种植体周围500μm外的骨质影响不大。②MicroCT可以三维再现种植体周围骨小梁结构,但种植体-骨结合界面受到金属伪影的干扰,故应与组织形态学互为补充。实验三纯钛种植体微/纳米表面对骨质疏松症骨结合的影响目的比较机械加工表面、微米机构表面及微/纳米结构表面三种类型的种植体在骨质疏松情况下对骨结合和生物力学性能的影响。方法通过去势、糖皮质激素加低钙饮食的方法建立绵羊颌骨骨质疏松模型,在8只骨质疏松的绵羊双侧下颌骨各植入三种类型的种植体(机械加工表面、微米机构表面及微/纳米复合结构表面),3个月后通过共振频率检测、MicroCT、组织形态计量学观察及生物力学的方法,检测三种表面形貌种植体在骨质疏松情况下对种植体骨结合和稳定性的影响。结果种植体植入三个月后,微/纳米表面组ISQ较机械加工组、微米表面组分别提高29.22%、28.17%(P <0.05),微/纳米表面组BIC较机械加工表面组、微米表面组分别提高47.51%、36.78%(P <0.05),微/纳米表面组最大拔出力较机械加工表面组最大拔出力、微米表面组分别提高34.41%、19.30%(P <0.05),微/纳米表面组BV/TV、Tb.Sp、TBPf与机械加工组、微米表面组比较差异均有显著性(P <0.05)。结论①颌骨骨质疏松情况下,种植体植入后可以形成骨结合,但骨结合率低于正常,生物力学性能下降。②颌骨骨质疏松情况下,种植体表面的微纳米结构可以有效的提高种植体的骨结合率,增加种植体的稳定性。

【Abstract】 Experiment 1 Establishment of a Postmenopausal Osteoporosis Ovine Jaw Model by OvariectomyObjective To study the time to establishment of an osteoporosis ovine jaw model through ovariectomy (OVX). To evaluate the micro-architectural and biomechanical changes of jaw bone after OVX and compare to other bones. Method 12 adult sheep were randomly divided into two groups: OVX group (n=7), sham-operated group (n=5). At the time of operation and after 12 months, all sheep underwent dual energy x-ray absorptiometry (DEXA) of jaw and lumbar vertebrae. 12 months after operation, all sheep were sacrificed. The trabecular bone (jaw, spine, femoral condyle, rib) and cortical bone (jaw) were harvested and compared by MicroCT. Axial compression tests were used to evaluate the mechanical properties of jaw. Results 12 months after operation, jaw BMD in OVX group decreased by 31.0% compared with that in control group (P < 0.05). The maxium compression strain of jaw in OVX group decreased by 34.2% compared with that in Sham group (P < 0.05). BV/TV、Tb.Th、Tb.N and Tb.Sp of trabecular bone decreased significantly (P <0.05). Histomorphologically, trabecular bone of jaw decreased significantly in OVX group compared with that in control group. Micro-fracture and micro-defect in trabecular bone of jaw could be seen in OVX group. Conclusions①Ovariectomy can establish post-menopausal osteoporosis ovine jaw model. The ovariectomized phase should be maintained 12 months at least to ensure the animal model could be established successfully.②The jaw osteoporosis could be found after OVX, though the bone loss in jaw occurs slower than that in spine.Experiment 2 Effect of hierarchical micro/nano surface titanium implant on osseointegrationObjective To investigate the effects of three morphologically differing titanium implants (machined surface, micro-textured surface, hierarchical micro/nano- textured surface) on osseointegration in ovine jaw. Method The machined surface of pure titanium implant was fabricated by acid in 0.5% (wt/v) hydrofluoric (HF) to form the micro-textured surface, then the micro-textured surface was further anodized in HF acid electrolytes to form the hierarchical micro/nano-textured surface. The three morphologically differing titanium implants were placed in ovine mandibles respectively. 3 months after implantation, resonance frequency analysis (RFA), MicroCT, histomorphometry and biomechanical tests were applied to detect the osseointegration of the three morphologically differing titanium implants. Results 3 months after implantation, the implant stability quotient (ISQ) values in micro/nano surface group increased by 15.47%, 11.50% compared with that in machined surface group and micro surface group (P <0.05). MicroCT analysis showed that there were significant differences between BV/TV, Tb.Sp and TBPf in the micro/nano group and that in machined surface group and micro surface group (P <0.05). The bone implant contact (BIC) increased by 34.07%, 23.15% compared with that in machined surface group and micro surface group (P <0.05). The maximum pull-out forces increased by 24.35%, 1.77% compared with that in machined surface group and micro surface group (P <0.05). Conclusions①Implant modification by HF acid etching and anodization to form a hierarchical micro/nano-textured surface could improve titanium implant osseointegration.②MicroCT images show 3D information of trabecular bone around implant clearly, which cannot be obtained using 2D histomorphometry. Due to the limitations of scanning at the tissue–implant interface, conventional histomorphometrical analysis and MicroCT are neither interchangeable, nor independent techniques, but need to be considered as complementary techniques.Experiment 3 Effect of hierarchical micro/nano surface titanium implant on osseointegration in ovariectomized sheepObjective To investigate the effects of three morphologically differing titanium implants (machined surface, micro-textured surface, hierarchical micro/nano- textured surface) on osseointegration in OVX ovine jaw. Method The machined surface of pure titanium implant was fabricated by acid in 0.5% (wt/v) hydrofluoric (HF) to form the micro-textured surface, then the micro-textured surface was further anodized in HF acid electrolytes to form the hierarchical micro/nano-textured surface. The three morphologically differing titanium implants were placed in mandibles of OVX sheep respectively. 3 months after implantation, resonance frequency analysis (RFA), MicroCT, histomorphometry and biomechanical tests were applied to detect the osseointegration of the three morphologically differing titanium implants. Results 3 months after implantation, the implant stability quotient (ISQ) values in micro/nano surface group increased by 29.22%, 28.17% compared with that in machined surface group and micro surface group (P <0.05). MicroCT analysis showed that there were significant differences between BV/TV, Tb.Sp and TBPf in the micro/nano group and that in machined surface group and micro surface group (P <0.05). The bone implant contact (BIC) increased by 47.51%, 36.78% compared with that in machined surface group and micro surface group (P <0.05). The maximum pull-out forces increased by 34.41%, 19.30 % compared with that in machined surface group and micro surface group (P <0.05). Conclusions①Osseointegration of dental implant can be achieved in osteoporotic bone, but it does worse than in normal bone.②Implant modification by HF acid etching and anodization to form a hierarchical micro/nano-textured surface could improve titanium implant osseointegration in OVX sheep.

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