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大鼠磨牙根周微观结构的仿真和验证

Simulation of Rat Molar Periodontal Microstructure in Orthodontic Tooth Movement

【作者】 许一起

【导师】 丁寅;

【作者基本信息】 第四军医大学 , 口腔临床医学, 2012, 博士

【摘要】 正畸力经牙齿传导至牙周组织,通过局部应力刺激和形变引发一系列的生物力学和分子生物学变化,使牙根压力侧和张力侧的牙槽骨分别发生骨吸收和骨生成,最终导致牙齿的移动正畸力作用下牙齿牙周膜和牙槽骨的宏观生物力学原理已经得到了较为广泛和深入的研究但是,以往的研究往往将牙槽骨作为各向同性和均质的整体进行研究,而忽视了根周牙槽骨微观结构的高度复杂性随着高精度CT成像技术的发展和应用,牙周膜腔硬骨板和围绕牙根,呈复杂立体网状排列的松质骨骨小梁得到了更为精密和直观的三维成像,这使我们认识到,对于这种以微米为单位的复杂微观结构在正畸载荷作用下的生物力学表现,我们还知之甚少具有不同形态特征的根周牙槽骨微观结构,尤其是骨质疏松状态下的牙槽骨,往往会对正畸负载产生不同的反应,这对正畸临床有着重要的指导作用因此,为了探讨加力初期松质骨的应力分布及机械形变,从而构建能够较好模拟其力学特性的仿真模型,我们设计并进行了如下实验:1.大鼠牙槽骨Micro-CT扫描及骨结构形态分析对雌性SD大鼠行Micro-CT扫描,观测健康及去势大鼠上颌第一磨牙根周牙槽骨的显微结构并测量其骨结构参数,以颈椎骨骨小梁为对照,从而分析健康大鼠和去势大鼠牙槽骨的微观形态特点2.健康大鼠磨牙正畸移动的动态Micro-CT扫描观测建立健康大鼠磨牙近中移动模型,在0天1天2天3天5天和7天六个时间点进行Micro-CT活体扫描,测量不同正畸力值(30g和100g)下磨牙牙周膜宽度及磨牙近中移动时位置和角度的改变,从而获知磨牙移动的规律3. OVX大鼠磨牙正畸移动的动态Micro-CT扫描观测建立OVX大鼠正畸加力(30g)模型,近中移动左侧上颌第一磨牙;在加力后六个时间点进行Micro-CT活体扫描,以假手术大鼠为对照,以测量不同牙槽骨状态下磨牙牙周膜宽度变化和磨牙近中移动时位置和角度改变4.大鼠磨牙根周微观仿真模型的建立根据实验一获得的大鼠磨牙根周牙槽骨骨小梁的骨结构参数建立单根骨小梁模型,继而搭建十四面体松质骨结构单元,建立个性化数字骨小梁网状构型,从而构建大鼠磨牙根周微观结构的仿真模型;根据实验二和实验三观测的大鼠磨牙受力及移动特点,设计相应的工况,观测仿真模型在正畸力作用下的应力分布和机械形变5.健康大鼠磨牙根周微观仿真模型正畸模拟的验证根据实验一获得的20只健康雌性SD大鼠上颌第一磨牙根周骨结构参数,建立20个正常仿真模型,分别对大鼠和仿真模型进行30g和100g正畸力的加载,观察加力后六个时间点大鼠和仿真模型骨小梁微观结构参数的变化,统计分析其差异以判断模型的仿真度6.去势大鼠磨牙根周微观仿真模型正畸模拟的验证根据20只去势SD大鼠上颌磨牙根周牙槽骨骨结构参数,建立20个OVX仿真模型,加载30g力,通过比较六个时间点仿真模型和OVX大鼠磨牙根周牙槽骨骨结构参数的差异,并与正常组仿真模型进行对照,统计分析其差异,以判断骨质疏松仿真模型的正畸加力仿真度结果发现:1.健康大鼠磨牙根周牙槽骨的骨体积分数(BV/TV)骨小梁数目(Tb.N)和结构模型指数(SMI)均明显高于颈椎,而骨小梁厚度(Tb.Th)和骨小梁间隙(Tb.Sp)明显低于颈椎(p<0.05),说明健康大鼠牙槽骨骨量高于颈椎,骨小梁更为细小OVX大鼠磨牙根周牙槽骨与颈椎的差异与健康大鼠相似OVX大鼠的BV/TV Tb.Th和Tb.N较健康大鼠下降,而Tb.Sp和SMI较健康大鼠升高,说明OVX大鼠牙槽骨骨量下降,骨小梁吸收明显2.健康大鼠磨牙正畸加力后,牙周膜宽度变化在0-2天明显,重力组作用下牙周膜宽度变化更为迅速,但2-5天两组差异不明显,5-7天轻力组牙周膜宽度有恢复趋势,而重力组没有重力组作用下磨牙近中移动更为明显,(p<0.05)不同正畸力值作用下,两组均没有明显垂直向位移和磨牙倾斜角度的改变3. OVX大鼠磨牙正畸加力后,牙周膜宽度的变化较对照组明显在5-7天健康大鼠磨牙牙周膜宽度出现恢复的趋势,而OVX大鼠没有,两组差异显著OVX大鼠磨牙近中位移程度大于对照组,在第3天和第5天差异有统计学意义(p<0.05) OVX大鼠在30g力作用下上颌第一磨牙没有明显的垂直向位移和磨牙倾斜角度的改变4.构建的模型较好的反映了健康和OVX大鼠磨牙根周牙槽骨骨小梁的结构形态特点;模拟了健康和OVX大鼠在正畸力(30g和100g)作用下大鼠磨牙根周微观结构的应力分布和机械形变,发现应力主要集中于骨小梁中段结构薄弱区和靠近牙根硬骨板的部位模型受力后出现压缩形变,其骨结构参数的变化规律与牙槽骨压缩形变相符5.在加力后的0-5天,不同力值作用下仿真模型对健康大鼠的模拟效果较好,5-7天仿真模型对健康大鼠各项骨结构参数变化的模拟效果均较差100g力作用下模型的仿真度整体低于30g力6.轻力作用下仿真模型对OVX大鼠磨牙根周牙槽骨的模拟效果在0-5天较好,5-7天各项指标差异明显,仿真效果较差OVX仿真模型的仿真度整体低于对照组结论:1.大鼠磨牙根周牙槽骨骨小梁微观结构与颈椎不同:健康大鼠牙槽骨磨牙根周骨小梁为混合式骨小梁,颈椎则为板状骨小梁;OVX大鼠磨牙根周牙槽骨较健康大鼠出现了明显的骨量下降,表现出骨质疏松的特征2.健康大鼠上颌磨牙加载正畸力后的0-2天磨牙的位移主要源于牙周膜的压缩和拉伸形变5-7天轻力(30g)作用下牙周膜宽度有恢复性变化趋势2-7天轻力(30g)和重力(100g)作用下磨牙均为整体近中移动,重力作用下磨牙近移更为明显3. OVX大鼠上颌磨牙加载正畸力后牙周膜宽度的变化较假手术大鼠明显,但5-7天牙周膜宽度没有出现恢复性变化趋势OVX大鼠磨牙受力后整体近中移动,近移程度大于对照组,但伴随着更长的近移停滞期4.构建了健康大鼠与OVX大鼠磨牙根周微观仿真模型模型能够对健康和OVX大鼠磨牙根周微观形态结构进行较好的形态模拟正常和OVX仿真模型在30g和100g力加载下,骨结构参数随时间出现了压缩形变的特征性变化趋势,并随着加力时间延长逐渐显著由于大鼠磨牙根周牙槽骨的压缩有一定限度,因此仿真模型只能在加载后的一定时间内进行力学模拟建立了仿真模型结构参数和松质骨结构参数的数值转换关系,为后续研究的开展打下了基础5.仿真模型在加力的0-5天能够较好的模拟健康大鼠磨牙根周牙槽骨微观结构的机械受力形变,但是随着大鼠磨牙根周牙槽骨受力后骨改建的逐渐活跃,仿真效果逐渐下降,说明构建的仿真模型不能体现正畸力作用下牙槽骨的长期复杂变化轻力加载下仿真模型的仿真度更高6. OVX模型在加载轻力后的短期内能够较好反映OVX大鼠磨牙根周牙槽骨骨小梁的机械受力变化,但是由于骨质疏松牙槽骨骨小梁对应力更为敏感,存在较明显的骨改建,因此其仿真度在5-7天明显下降

【Abstract】 Orthodontic force acts on periodontal structures through teeth crown androots, during which induces a series of biomechanical and molecular biologicalchanges through local stress stimuli and deformation. Tooth movement is theresult of bone resorption on the pressure side as well as bone osteogenesis on thetension side. The macroscopic biomechanics of teeth, periodontal membrane andalveolar bone has been investigated thoroughly. However, researchers treatedalveolar bone as isotropic and homogeneous material and ignored the fact thatperiodontal microstructure around roots is highly complex and inhomogeneous.After the development and application of high-resolution Micro-CT, moreaccurate three-dimensional photograph of periodontal membrane, lamina duraand trabecular net structure can be achieved, which make researchers realizedthat how little we know about the biomechanics of periodontal microstructuresin this level. Different kind of alveolar, especially alveolar under osteoporosis,has different reactions towards orthodontic treatment, by learning which willhelp clinical practitioners a lot. Thus, we establish a finite elemental model tosimulate microstructure around molar root of rat. My research consists of5steps:1. Morphological analysis of alveolar bone of SD rats through Micro-CT scanningArchive bone feature parameters of maxillary alveolar bone around firstmolar roots and cervical vertebra by female SD rats Micro-CT scanning toperform alveolar bone morphological analysis, especially osteoporotic alveolarbone.2. An in vivo Micro-CT observation of molar movement under orthodontictreatment in healthy SD ratsBuild healthy rats molar mesial movement model (30g VS.100g). Throughin vivo Micro-CT scanning at0d,1d,2d,3d,5d and7d, periodontal ligamentthickness, molar displacement and angular changes were recorded, throughwhich molar movement pattern can be learnt.3. An in vivo Micro-CT observation of molar movement under orthodontictreatment in OVX ratsBuild osteoporotic rats molar mesial movement model (30g). Use in vivoMicro-CT scanning at0d,1d,2d,3d,5d and7d to register periodontal ligamentthickness and molar movement pattern.4. Establishment of periodontal microstructure simulation model around ratmolarBuild trabecular unit model according to bone feature parameters achievedin step1. Establish trabecular tetrakaidecahedral unit to simulate individualcancellous bone net structure. Then assemble molar root, periodontal membrane,lamina dura and trabecular net structure together; construct simulation modelworking condition on the basis of molar stress distribution and movementdiscipline in step2to observe model stress distribution and mechanicaldeformation under orthodontic force load.5. Orthodontic simulation model verification of healthy rats Build20individual simulation models according to20healthy female SDrats maxillary alveolar bone feature parameters. Then load30g and100gorthodontic force to rats and models respectively. Observe rats bone featureparameters longitudinal changes at0d,1d,2d,3d,5d and7d, then compare withmodels parameters at the same time points. Analyze the difference between ratsand models to testify the simulation degrees.6. Orthodontic simulation model verification of OVX ratsBuild20osteoporotic simulation models according to20osteoporoticfemale SD rats maxillary alveolar bone feature parameters.30g force wasloaded on rats and models to compare the difference. Analyze the differencebetween osteoporotic rats and models to testify the simulation degrees.Results:1. BV/TV, Tb.N and SMI in healthy rat maxillary alveolar bone are higher thanin cervical vertebra, while Tb.Th and Tb.Sp are lower than in cervicalvertebra. BV/TV, Tb.Th and Tb.N of OVX rats alveolar bone decreasedsignificantly comparing with healthy rats while Tb.Sp and SMI increasedobviously. In OVX group, cervical vertebra bone volume fraction decreased50.5%compare with healthy rats, while alveolar bone volume fractiondecreased only29.8%.2. PDL thickness changes can be observed immediately after force loading,however, there are difference between light and heavy force. The100g forcecan cause PDL thickness changes in a shorter time. Molar mesial movementcan be observed in both groups.100g force induced more movement than30g and followed by a longer lag period.30g force has shorter lag periodand molar continues to move forward after day5. Healthy rats molar has abodily movement pattern and no obvious rotation and inclination. 3. PDL width change in OVX rats is similar to healthy rats. However, OVX ratPDL width doesn’t has recover trend like healthy rats. We can observe moremolar mesial movement in OVX rats than in healthy rats. OVX rats molarhas a bodily movement pattern.4. Simulation model can represent the morphological characteristics of healthyand osteoporotic alveolar bone. Then the simulation of orthodontic force(30g and100g) on normal model shows characteristic stress distribution andmechanical deformation.5. Simulation models kept good consistency with healthy rats during0-5daysafter loading. On day7, every features simulation decreased obviously. Thesimulation degree is lower under100g force than30g force.6. The results are similar with healthy rats simulation. OVX models have goodconsistency with rats suffering osteoporosis during0-5days after forceloading (30g). On day7, features are obvious different between OVX ratsand models. The simulation degree is lower in OVX models than in controlgroups.Conclusions:1. Alveolar bone features in rats has its own characteristics comparing withvertebra bone: trabecular around molar roots are mixture of both plate-likeand rod-like trabecular and cervical vertebra trabecular are mainly plate-like.Bone volume fraction in OVX rat alveolar bone decreased significantly,however, the decreasing degree is not as much as the one in cervicalvertebra.2. The upper first molar of healthy rats moves bodily during0-7days afterorthodontic force loading.30g force can induce PDL width recoveringduring5d-7d.100g force can induce more obvious molar mesial movement. 3. Molar movement pattern in OVX rats are similar to health rats. OVX ratsdoesn’t have PDL width recover trend and have more obvious molarmovement than healthy rats.4. The simulation model shows similar micro structure with rats alveolararound molar roots. The model has infinite deformation trend after forceloading compared with rats actual measurement. The model morphology canbe transferred to cancellous bone parameter in math language.5. Results show that the consistence is high during0-5days then decreasedalong with the bone remodeling activation. On day7, the consistencedecreased significantly both in light force groups and heavy force ones,which indicates models lack of biological analogue couldn’t simulate thecomplicated alveolar bone changes under long-term orthodontic forceloading. The simulation degree is higher under30g force than100g force.6. Similar to healthy rats simulation, osteoporotic model can analogue themechanical deformation under short-term force loading. However,osteoporotic alveolar bone is usually more sensitive to force loading,especially the heavy one. So simulation model could only analogueosteoporotic rats under short-term orthodontic force loading.

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