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
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 scanning
Archive 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 rats
Build 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 ratmolar
Build 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 rats
Build20osteoporotic 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.
引文
[1] Draper ER, Morris MD, Camacho NP, Matousek P, Towrie M, Parker AW,Goodship AE. Novel assessment of bone using time-resolvedtranscutaneous Raman spectroscopy. J Bone Miner Res.2005;20:1968–1972.
[2] Genant HK, Engelke K, Prevrhal S. Advanced CT bone imaging inosteoporosis. Rheumatology (Oxford).2008;47(Suppl4): iv9–iv16.
[3] Avery NC, Sims TJ, Bailey AJ. Quantitative determination of collagencross-links. Methods Mol Biol.2009;522:103–121.
[4] Genant HK, Engelke K, Prevrhal S. Advanced CT bone imaging inosteoporosis. Rheumatology (Oxford).2008;47(Suppl4): iv9–iv16.
[5] Cummings SR, Black DM, Rubin SM. Lifetime risks of hip, Colles’, orvertebral fracture and coronary heart disease among white postmenopausalwomen. Arch Intern Med.1989;149:2445–2448.
[6] Cummings SR, Black DM, Rubin SM. Lifetime risks of hip, Colles’, orvertebral fracture and coronary heart disease among white postmenopausalwomen. Arch Intern Med.1989;149:2445–2448.
[7] Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ,Ott SM, Recker RR. Bone histomorphometry: standardization ofnomenclature, symbols, and units. Report of the ASBMRHistomorphometry Nomenclature Committee. J Bone Miner Res.1987;2:595–610.
[8] Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M. Thedirect examination of three-dimensional bone architec-ture in vitro bycomputed tomography. J Bone Miner Res.1989;4:3–11.
[9] Ruegsegger P, Koller B, Muller R. A microtomographic system for thenondestructive evaluation of bone architecture. Calcif Tissue Int.1996;58:24–29.
[10]Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment oftrabecular bone microarchitecture by high-resolution peripheralquantitative computed tomography. J Clin Endocrinol Metab.2005;90:6508–6515.
[11]Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M,Peterson JM, Melton LJ3rd. Effects of sex and age on bone microstructureat the ultradistal radius: a population-based noninvasive in vivo assessment.J Bone Miner Res.2006;21:124–131.
[12]Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M,Peterson JM, Melton LJ3rd. Effects of sex and age on bone microstructureat the ultradistal radius: a population-based noninvasive in vivo assessment.J Bone Miner Res.2006;21:124–131.
[13]Feldkamp LA, Davis LC, Kress JW. Practical cone-beam algorithm. J OptSoc Am A.1984;1:612–619.
[14]Berger MJ, Hubbell JH, Seltzer SM, Chang J, Coursey JS, Sukumar R,Zucker DS. XCOM: Photon Cross Sections Data-base. Gaithersburg, MD:National Institute of Standards and Technology;1990.
[15]Faulkner KG, Gluer CC, Grampp S, Genant HK. Cross-calibration of liquidand solid QCT calibration standards: cor-rections to the UCSF normativedata. Osteoporos Int.1993;3:36–42.
[16]Graeff W, Engelke K. Microradiography and microtomography. In: EbashiS, Koch M, Rubenstein E, eds. Handbook on Syn-chrotron Radiation4.New York, NY: Elsevier Science;1991:361–405.
[17]Ito M, Ejiri S, Jinnai H, Kono J, Ikeda S, Nishida A, Uesugi K, Yagi N,Tanaka M, Hayashi K. Bone structure and mineraliza-tion demonstratedusing synchrotron radiation computed tomography (SR-CT) in animalmodels: preliminary findings. J Bone Miner Metab.2003;21:287–293.
[18]Kinney JH, Haupt DL, Ladd AJ. Applications of synchrotronmicrotomography in osteoporosis research. Proc SPIE.1997;3149:64–68.
[19]Salome M, Peyrin F, Cloetens P, Odet C, Laval-Jeantet AM, Baruchel J,Spanne P. A synchrotron radiation microtomography system for the analysisof trabecular bone samples. Med Phys.1999;26:2194–2204.
[20]Tzaphlidou M, Speller R, Royle G, Griffiths J, Olivo A, Pani S, Longo R.High resolution Ca/P maps of bone architecture in3D synchrotron radiationmicrotomographic images. Appl Radiat Isot.2005;62:569–575.
[21]Ruegsegger P, Koller B, Muller R. A microtomographic system for thenondestructive evaluation of bone architecture. Calcif Tissue Int.1996;58:24–29.
[22]Scanco Medical AG. Scanco lCT50.2010. Available at:http://www.scanco.ch/systems-solutions/specimen-systems/uct-50. html.Accessed August1,2010.
[23]SkyScan. SkyScan1172high-resolution micro-CT.2010. Avail-able at:http://www.skyscan.be/products/1172.htm. Accessed August1,2010.
[24]Xradia. MicroXCT400.2010. Available at: http://xradia.com/products/microxct-400.php. Accessed August1,2010.
[25]Waarsing JH, Day JS, van der Linden JC, Ederveen AG, Spanjers C, DeClerck N, Sasov A, Verhaar JA, Weinans H. Detecting and tracking localchanges in the tibiae of individual rats: a novel method to analyselongitudinal in vivo micro-CT data. Bone.2004;34:163–169.
[26]Gasser JA, Ingold P, Grosios K, Laib A, Hammerle S, Koller B.Noninvasive monitoring of changes in structural cancellous boneparameters with a novel prototype micro-CT. J Bone Miner Metab.2005;23(Suppl):90–96.
[27]Mulder L, Koolstra JH, Van Eijden TM. Accuracy of microCT in thequantitative determination of the degree and distribution of mineralizationin developing bone. Acta Radiol.2004;45:769–777.
[28]Meganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA. Beamhardening artifacts in micro-computed tomography scanning can be reducedby X-ray beam filtration and the resulting images can be used to accuratelymeasure BMD. Bone.2009;45:1104–1116.
[29]Ito M, Ejiri S, Jinnai H, Kono J, Ikeda S, Nishida A, Uesugi K, Yagi N,Tanaka M, Hayashi K. Bone structure and mineraliza-tion demonstratedusing synchrotron radiation computed tomography (SR-CT) in animalmodels: preliminary findings. J Bone Miner Metab.2003;21:287–293.
[30]Meganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA. Beamhardening artifacts in micro-computed tomography scanning can be reducedby X-ray beam filtration and the resulting images can be used to accuratelymeasure BMD. Bone.2009;45:1104–1116.
[31]Kazakia GJ, Burghardt AJ, Cheung S, Majumdar S. Assessment of bonetissue mineralization by conventional x-ray microcom-puted tomography:comparison with synchrotron radiation microcomputed tomography and ashmeasurements. Med Phys.2008;35:3170–3179.
[32]Fajardo RJ, Cory E, Patel ND, Nazarian A, Laib A, Manoharan RK,Schmitz JE, DeSilva JM, MacLatchy LM, Snyder BD, Bouxsein ML.Specimen size and porosity can introduce error into microCT-based tissuemineral density measurements. Bone.2009;44:176–184.
[33]Meganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA. Beamhardening artifacts in micro-computed tomography scanning can be reducedby X-ray beam filtration and the resulting images can be used to accuratelymeasure BMD. Bone.2009;45:1104–1116.
[34]Burghardt AJ, Kazakia GJ, Laib A, Majumdar S. Quantita-tive assessmentof bone tissue mineralization with polychro-matic micro-computedtomography. Calcif Tissue Int.2008;83:129–138.
[35]Kazakia GJ, Burghardt AJ, Cheung S, Majumdar S. Assessment of bonetissue mineralization by conventional x-ray microcom-puted tomography:comparison with synchrotron radiation microcomputed tomography and ashmeasurements. Med Phys.2008;35:3170–3179.
[36]Goulet RW, Goldstein SA, Ciarelli MJ, Kuhn JL, Brown MB, Feldkamp LA.The relationship between the structural and orthogonal compressiveproperties of trabecular bone. J Bio-mech.1994;27:375–389.
[37]Hildebrand T, Laib A, Muller R, Dequeker J, Ruegsegger P. Directthree-dimensional morphometric analysis of human cancellous bone:microstructural data from spine, femur, iliac crest, and calcaneus. J BoneMiner Res.1999;14:1167–1174.
[38]Hildebrand T, Ruegsegger P. A new method for the model-independentassessment of thickness in three-dimensional ima-ges. J Microsc.1997;185:67–75.
[39]Harrigan TP, Mann RW. Characterization of microstructural anisotropy inorthotropic materials using a second rank tensor. J Mater Sci.1984;19:761–767.
[40]Odgaard A, Kabel J, van Rietbergen B, Dalstra M, Huiskes R. Fabric andelastic principal directions of cancellous bone are closely related. J Biomech.1997;30:487–495.
[41]Odgaard A, Gundersen HJ. Quantification of connectivity in cancellousbone, with special emphasis on3-D reconstructions. Bone.1993;14:173–182.
[42]Hildebrand T, Ruegsegger P. Quantification of bone microar-chitecturewith the Structure Model Index. Comput Methods Biomech Biomed Engin.1997;1:15–23.
[43]Liu XS, Sajda P, Saha PK, Wehrli FW, Bevill G, Keaveny TM, Guo XE.Complete volumetric decomposition of individual trabecular plates and rodsand its morphological correlations with anisotropic elastic moduli in humantrabecular bone. J Bone Miner Res.2008;23:223–235.
[44]Peyrin F, Attali D, Chappard C, Benhamou CL. Local plate/rod descriptorsof3D trabecular bone micro-CT images from medial axis topologic analysis.Med Phys.2010;37:4364–4376.
[45]Stauber M, Muller R. Volumetric spatial decomposition of tra-becular boneinto rods and plates—a new method for local bone morphometry. Bone.2006;38:475–484.
[46]van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method todetermine trabecular bone elastic properties and loading usingmicromechanical finite-element models. J Bio-mech.1995;28:69–81.
[47]Muller R, Ruegsegger P. Three-dimensional finite element modelling ofnon-invasively assessed trabecular bone structures. Med Eng Phys.1995;17:126–133.
[48]Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecularbone. Annu Rev Biomed Eng.2001;3:307–333.
[49]van Rietbergen B. Micro-FE analyses of bone: state of the art. Adv ExpMed Biol.2001;496:21–30.
[50]Stauber M, Rapillard L, van Lenthe GH, Zysset P, Müller R. Importance ofindividual rods and plates in the assessment of bone quality and their contri-bution to bone stiffness. J Bone Miner Res2006;21(4):586–595.
[51]D’Urso, P. S., R. L. Atkinson, M. W. Lanigan, W. J. Earwaker, I. J. Bruce, A.Holmes, T. M. Barker, D. J. Effeney, and R. G. Thompson.Stereolithographic (SL) biomodelling in craniofa-cial surgery. Br. J. Plast.Surg.51(7):522–530,1998.
[52]Liebschner, M. A. K. Biomechanical considerations of ani-mal models usedin tissue engineering of bone. Biomaterials25(9):1697–1714,2004.
[53]Mu l ler, R., H. Van Campenhout, B. Van Damme, G. Van der Perre, J.Dequeker, T. Hildebrand, and P. Ru e gsegger. Morpho-metric analysis ofhuman bone biopsies: A quantitative struc-tural comparison of histologicalsections and micro-computed tomography. Bone23(1):59–66,1998.
[54]Engelke, K., C. Su, and W. A. Kalender. Stereolithographic modelssimulating trabecular bone and their characterization by thin-slice andmicro-CT. Eur. Radiol.11(10):2026–2040,2001.
[55]Jones, J. R., and L. L. Hench. Regeneration of trabecular bone using porousceramics. Curr. Opin. Solid State Mater. Sci.7(4–5):301–307,2003.
[56]Sun, W., B. Starly, A. Darling, and C. Gomez. Computer-aided tissueengineering: Application to biomimetic modelling and design of tissuescaffolds. Biotechnol. Appl. Biochem.39(1):49–58,2004.
[57]Lam,C.X.F.,X.M.Mo,S.H.Teoh,andD.W. Hutmacher. Scaffold developmentusing3D printing with a starch-based polymer. Mater. Sci. Eng. C20(1–2):49–56,2002.
[58]Hutmacher, D. W. Scaffolds in tissue engineering bone and car-tilage.Biomaterials21(24):2529–2543,2000.
[59]Kalita, S. J., S. Bose, H. L. Hosick, and A. Bandyopadhyay. Developmentof controlled porosity polymer–ceramic compos-ite scaffolds via fuseddeposition modeling. Mater. Sci. Eng. C23(5):611–620,2003.
[60]Zein, I., D. W. Hutmacher, K. C. Tan, and S. H. Teoh. Fused depositionmodeling of novel scaffold architectures for tissue engineering applications.Biomaterials23(4):1169–1185,2002.
[61]Leong, K. F., C. M. Cheah, and C. K. Chua. Solid freeform fabrication ofthree-dimensional scaffolds for engineering re-placement tissues andorgans. Biomaterials24(13):2363–2378,2003.
[62]Landers, R., U. Hubner, R. Schmelzeisen, and R. Mulhaupt. Rapidprototyping of scaffolds derived from thermoreversible hydrogels andtailored for applications in tissue engineering. Biomaterials23(23):4437–4447,2002.
[63]Taboas, J. M., R. D. Maddox, P. H. Krebsbach, and S. J. Hollister. Indirectsolid free form fabrication of local and global porous, biomimetic andcomposite3D polymer–ceramic scaffolds. Bio-materials24(1):181–194,2003.
[64]Xiong, Z., Y. Yan, S. Wang, R. Zhang, and C. Zhang. Fabrication of porousscaffolds for bone tissue engineering via low-temperature deposition. Scr.Mater.46(11):771–776,2002.
[65]Zysset, P. K., A. L. Marsan, T.-M. G. Chu, R. E. Guldberg, J. W. Halloran,and S. J. Hollister. Rapid prototyping of trabecular bone for mechanicaltesting. In: Proceedings of the Bioengi-neering Conference. Sunriver, OR,USA: American Society of Mechanical Engineers, Bioengineering Division(Publication) BED,1997.
[66]Borah, B., G. Gross, T. Dufresne, T. Smith, M. Cockman, P. Chmielewski,M. Lundy, J. Hartke, and E. Sod. Three-dimensional microimaging (MRμIand μCT), finite element modeling, and rapid prototyping provide uniqueinsights into bone architecture in osteoporosis. Anat. Rec.(New Anat.)265(2):101–110,2001.
[67]Engelke, K., C. Su, and W. A. Kalender. Stereolithographic modelssimulating trabecular bone and their characterization by thin-slice andmicro-CT. Eur. Radiol.11(10):2026–2040,2001.
[68]Burg, K. J. L., S. Porter, and J. F. Kellam. Biomaterial develop-ments forbone tissue engineering. Biomaterials21(23):2347–2359,2000.
[69]Cancedda, R., B. Dozin, P. Giannoni, and R. Quarto. Tissue engineering andcell therapy of cartilage and bone. Matrix Biol.22(1):81–91,2003.
[70]Davis, M. W., and J. P. Vacanti. Toward development of an im-plantabletissue engineered liver. Biomaterials17(3):365–372,1996.
[71]Leyh, R. G., M. Wilhelmi, T. Walles, K. Kallenbach, P. Rebe, A. Oberbeck,T. Herden, A. Haverich, and H. Mertsching. Acellu-larized porcine heartvalve scaffolds for heart valve tissue engi-neering and the risk ofcross-species transmission of porcine en-dogenous retrovirus. J. Thorac.Cardiovasc. Surg.126(4):1000–1004,2003.
[72]Perry, T. E., S. Kaushal, F. W. H. Sutherland, K. J. Guleserian, J. Bischoff,M. Sacks, and J. E. Mayer. Bone marrow as a cell source for tissueengineering heart valves. Ann. Thorac. Surg.75(3):761–767,2003.
[73]Sodian, R., S. P. Hoerstrup, J. S. Sperling, S. H. Daebritz, D. P. Martin, F. J.Schoen, J. P. Vacanti, and J. E. Mayer, Jr. Tissue engineering of heart valves:In vitro experiences. Ann. Thorac. Surg.70(1):140–144,2000.
[74]Ratcliffe, A. Tissue engineering of vascular grafts. Matrix Biol.19(4):353–357,2000.
[75]Niklason, L. E., and R. S. Langer. Advances in tissue engi-neering of bloodvessels and other tissues. Transplant Immunol.5(4):303–306,1997.
[76]Kadner, A., S. P. Hoerstrup, J. Tracy, C. Breymann, C. F. Maurus, S.Melnitchouk, G. Kadner, G. Zund, and M. Turina. Human umbilical cordcells: A new cell source for cardiovascular tissue engineering. Ann. Thorac.Surg.74(4):1422–1428,2002.
[77]Chen, M. K., and S. F. Badylak. Small bowel tissue engineering using smallintestinal submucosa as a scaffold. J. Surg. Res.99(2):352–358,2001.
[78]Hafemann, B., S. Ensslen, C. Erdmann, R. Niedballa, A. Zuhlke, K.Ghofrani, and C. J. Kirkpatrick. Use of a collagen/elastin-membrane for thetissue engineering of dermis. Burns25(5):373–384,1999.
[79]Flynn, L., P. D. Dalton, and M. S. Shoichet. Fiber templating ofpoly(2-hydroxyethyl methacrylate) for neural tissue engineer-ing.Biomaterials24(23):4265–4272,2003.
[80]Gibson, L.J., Ashby, M.F.,1997. Cellular Solids: Structure and Properties,second ed. Cambridge University Press, Cambridge.
[81]Gibson, L.J., Ashby, M.F.,1997. Cellular Solids: Structure and Properties,second ed. Cambridge University Press, Cambridge.
[82]Jensen, K.S., Mosekilde, L., Mosekilde, L.,1990. A model of vertebraltrabecular bone architecture and its mechanical properties. Bone11,417–423.
[83]Silva, M.J., Gibson, L.J.,1997a. The effects of non-periodic microstructureand defects on the compressive strength of two-dimensional cellular solids.International Journal of Mechanical Sciences39,549–563.
[84]Vajjhala, S., Kraynik, A.M., Gibson, L.J.,2000. A cellular solid model formodulus reduction due to resorption of trabeculae in bone. Journal ofBiomechanical Engineering122,511–515.
[85]Guo, X.E., Kim, C.H.,1999. Effects of age-related bone loss: A3Dmicrostructural simulation. Proceedings of the1999BioengineeringConference American Society of Mechanical Engineers Bioengi-neeringDivision, vol42. pp.327–328.
[86]Guo, X.E., Kim, C.H.,2002. Mechanical consequence of trabecular boneloss and its treatment: A three-dimensional model simulation. Bone30,404–411.
[87]Chen, C.S., Yannas, I.V., Spector, M.,1995. Pore strain behavior ofcollagen-glycosaminoglycan analogues of extracellular matrix. Biomaterials16,777–783.
[88]Yannas, I.V., Lee, E., Orgill, D.P., Skrabut, E.M., Murphy, G.F.,1989.Synthesis and characterization of a model extracellular matrix that inducespartial regeneration of adult mammalian skin. Proceedings of the NationalAcademy of Science USA86,933–937.
[89]Mikos, A.G., Bao, Y., Cima, L.G., Ingber, D.E., Vacanti, J.P., Langer, R.,1993. Preparation of poly (glycolic acid) bonded fiber structures for cellattachment and transplantation. Journal of Biomedical Materials Research27,183–189.
[90]Lu, L., Mikos, A.G.,1996. The importance of new processing techniques intissue engineering. Materials Research Society Bulletin21(11),28–31.
[91]Mikos, A.G., Thorsen, A.J., Czerwonka, L.A., Bao, Y., Winslow, D.N.,Vacanti, J.P., Langer, R.,1994. Preparation and character-ization of poly(L-lactic acid) foams. Polymer35,1068–1077.
[92]James, K., Kohn, J.,1996. New biomaterials for tissue engineering.Materials Research Society Bulletin21(11),22–26.
[93]Lhommeau, C., Levene, H., Abramson, S., Kohn, J.,1998. Prepara-tion ofhighly interconnected porous tyrosine-derived polycarbo-nate scaffolds.Tissue Engineering4,468.
[94]Müller R, Van Campenhout H, Van Damme B, Van Derperre G, Dequeker J,et al. Morphometric Analysis of Human Bone Biopsies: A QuantitativeStructural Comparison of Histological Sections and Micro ComputedTomography [J]. Bone,1998,23:59～66.
[95]Day J, Ding M, Odgaard A, Sumner D. Parallel Plate Model for TrabecularBone Exhibits Volume Fraction-Dependent Bias[J]. Bone,2000,27:715～720.
[96]Rude RK, Gruber HE, Norton HJ, et al. Bone loss induced by dietarymagnesium reduction to10%of the nutrient requirement in rat is associatedwith increased release of substance P and tumor necrosis factor-α[J]. TheJournal of Nutrition,2004,134:79～85.
[97]YAN Wei. China Medical Equipment,2005,2(3):31.
[98]LIU Guang-peng. Journal of Tissue Engineering and ReconstructiveSurgery,2006,2(4):228.
[99]Matsuura M, Lounici S, Inoue N, et al. Assessment of external fixatorreusability using load-and cycle-dependent tests[J]. Clin Orthop,2003,1(406):275-281.
[100] Moorcroft CI, Thomas PB, Verborg S, et al. Cortex distraction forcescaused by the insertion of external fixator pins[J]. Orthop Trauma,2001,15(7):507-512.
[101] Feldkamp LA, Goldstein SA, Parfitt AM, et al. Journal of Bone andMineral Research,1989,4:3.
[102] Akhter MP, Lappe JM, Davies KM, et al. Transmenopausal Changes inthe Trabecular Bone Structure [J]. Bone,2007,41:111-116.
[103] Kaplan JR, Manuck SB, Anthony MS, et al. Premenopausal socialstatus and hormone exposure predict postmenopausal atherosclerosis infemale monkeys [J]. Obstet Gynecol,2002,99(3):381-388.
[104] Whalen JP, Krook L. Periodental disease asan early manifestation ofosteoporosis[J]. Nutrition,1996,12(1):53-54.
[105]董福生,李增宁,董玉英,等.大鼠卵巢去势后颌骨与全身骨的形态学研究[J].现代口腔医学杂志,2002,16(6):499-500.
[106] FujimotoT, Nimi A, Sawai T, et al. Effectsof steroid-inducedosteoporosis on osseointegrtion of titaniumimplants [J]. Int J OralMaxillofacImplants,1998,13(2):183-189.
[107] Thomas K, Nasser P, Hasan A, et al. Stress analysis of bone modelingresponse to rat molar orthodontics. J. Biomechanics,1995,28(1):27-38.
[108] Rodrigo V, Thomas K, Jie C, et al. Three-dimensional mechanicalenvironment of orthodontic tooth movement and root resorption. Am JOrthod Dentofacial Orthop2008;133:791. e11-791. e26.
[109] S. Steigman, Y. Michaeli, M. Weinreb. Structural changes in the dentaland periodontal tissues of the rat incisor following application oforthodontic loads. Am J Orthod Dentofac Orthop,91(1987), pp.41-56.
[110] Carmen G, Hitoshi H, Yoshinori A, Tadashi N, etc. An in vivo3DMicro-CT evaluation of tooth movement after the application of differentforce magnitudes in rat molar. Angle Orthod.2009;79:703-714.
[111] Yamashino T, Sakuda M, Takano-yamamoto, et al. Experimental toothmovement in ovariectomized rats. J Dent Res,1994,73:148.
[112] Gonzales C, Hotokezaka H, Yoshimatsu M, Yozgatian JH, DarendelilerMA, Yoshida N. Force magnitude and duration effects on amount of toothmovement and root resorption in the rat molar. Angle Orthod.2008;78:502–509.
[113] Ren Y, Maltha J C, Kuijpers-Jagtman A M. Optimum force magnitudefor orthodontic tooth movement:a systematic literature review. AngleOrthodontist,2003a,73:86-92.
[114] Ren Y, Maltha J C, Van’t Hof M A, Kuijpers-Jagtman A M. Age effecton orthodontic tooth movement in rats. Journal of Dental Research,2003b,82:38-42.
[115] Melsen B. Biological reaction of alveolar bone to orthodontic toothmovement. Angle Orthodontist,1999,69:151-158.
[116] Wronski TJ, Dann LM, Horner SL. The study of osteoporosis model inrats. Bone,1989;10(3):295-304.
[117] Nishimura I, Hoskawa R, Kaplan ML, et al. Animal model forevaluating the effects of systemic estrogen deficiency on residual ridgeresorption. Prosthet Dent,1995;73(3):304-310.
[118]杨美祥,丁寅,徐如生,邹邦新.骨质疏松大鼠正畸牙齿的移动. JFourth Mil Med Univ,1999;20(7):628-629.
[119]杨美祥,丁寅,邹邦新,金作霖.骨质疏松大鼠正畸牙齿移动中牙周组织超微结构的变化. J Fourth Mil Med Univ,2003;24(1):30-31.
[120]谭理军,王军,赵志河等.骨质疏松老年大鼠正畸牙移动实验. JSichuan Univ(Med Sci Edi),2006;37(3):449-451.
[121] Tripuwabhrut P, Brudvik P, Fristad I, Rethnam S.Experimentalorthodontic tooth movement and extensive root resorption: periodontal andpulpal changes. Eur J Oral Sci.2010;118(6):596-603.
[122] Olson C, Uribe F, Kalajzic Z, Utreja A, Nanda R, Rowe D, WadhwaS.Orthodontic tooth movement causes decreased promoter expression ofcollagen type1, bone sialoprotein and alpha-smooth muscle actin in theperiodontal ligament.Orthod Craniofac Res.2012;15(1):52-61.
[123] pela S, Tomaz V, Andrej C, Martina D, Gorazd D. The endothelinsystem mediates bone modeling in the late stage of orthodontic toothmovement in rats. Bone,2008;43(4):40-747.
[124] Thomas K, Nasser P, Hasan A, et al. Stress analysis of bone modelingresponse to rat molar orthodontics. J. Biomechanics,1995,28(1):27-38.
[125] C. Bourauel, A. Kawarizadeh, W. G tz, A. J ger. Orthodontic toothmovement: Mechanical stimulus, cellular reactions and numerical boneremodeling simulation. Journal of Biomechanics, Volume39, Supplement1,2006, Page S414.
[126] Gefen A, Seliktar R. Comparison of the trabecular architecture and theisostatic stress flow in the human calcaneus. Med Eng Phys2004;26:119–29.
[127] Gefen A, Neulander R. Computational determination of the criticalmicrocrack size which causes a remodeling response in a trabecula: afeasibility study. J Appl Biomech2007;23:230–7.
[128] GefenA, Portnoy S, Diamant I. Inhomogeneity of tissue-level straindistributions in individual trabeculae: Mathematical model studies ofnormal and osteoporosis cases [J]. Medical Engineering&Physics,2008,30(5):624–630.
[129] Dagan D, Be'ery M, Gefen A. Single-trabecula building block forlarge-scale finite element models of cancellous bone. Med Biol Eng Comput2004;42:549–56.
[130] Thomas R K, Nasser H P, Hasan U A. Stress analysis of bone modelingresponse to rat molar orthodontics. J Biomechanics1995;28:27–38,.
[131] T. Hildebrand, P. Rüegesegger. Structure Model Index–A NewMethod to Describe Remodeling of Trabecular Bone [J]. Bone,1996,supplement,19(3):143.
[132] Wolff JL. The Law of Bone Remodeling. Berlin: Springer;1986(translation of the German1892original edition).
[133] Gefen A, Seliktar R. Comparison of the Trabecular Architecture and theIsostatic Stress Flow in the Human Calcaneus. Med Eng Phys,2004;26:119-129.
[134] McNamara L, Van der Linden J, Weinans H, Prendergast P.Stress-concentrating Effect of Resorption Lacunae in Trabecular Bone. JBiomech,2006;39:734-741.
[135] Smit TH, Burger EH. Is BMU-coupling a Strain-RegulatedPhenomenon? A Finite Element Analysis. J Bone Miner Res,2000;15:301-307.
[136] GefenA, Portnoy S, Diamant I. Inhomogeneity of tissue-level straindistributions in individual trabeculae: Mathematical model studies ofnormal and osteoporosis cases [J]. Medical Engineering&Physics,2008,30(5):624–630.
[137] Vajjhala, S., Kraynik, A. M., and Gibson, L. J. A Cellular Solid Modelfor Modulus Reduction due to Resorption of Trabeculae in Bone. J BiomechEng,2000;122:511-515.
[138] T.Guillen, Q.-H. Zhang, G. Tozzi, A. Ohrndorf, et al. Compressivebehavior of bovine cancellous bone and bone analogous materials, microCTcharacterization and FE analysis. Journal of the Mechanical Behavior ofBiomedical Materials.2011,4:1452-1461.
[139] Gianluca Tozzi, Qing-Hang Zhang, Jie Tong.3D Real-timeMicromechanical Compressive Behaviour of Bone-cement Interface:Experimental and Finite Element Studies. J Biomech,2012,45:356-363.
[140] Sargent R G. Validation and Verification of Simulation Models [C].Proceedings of the Simulation Conference,2004:5-8.
[141] Brade D. Enhancing Modeling and Simulation Accreditation byStructuring Verification and Validation Results [C]. Proceedings of theSimulation Conference,2000:840-848.
[142] Müller R, Van Campenhout H, Van Damme B, Van Derperre G,Dequeker J, et al. Morphometric Analysis of Human Bone Biopsies: AQuantitative Structural Comparison of Histological Sections andMicro-Computed Tomography [J]. Bone,1998,23:59-66.
[143] Ding M, Odgaard A, Hvid I. Accuracy of Cancellous Bone VolumeFraction Measured by Micro-CT Scanning [J]. J Biomech,1999,32:323-326.
[144] Link TM, Majumdar S, Lin JC, et al. Assessment of TrabecularStructure Using High Resolution CT Images and Texture analysis. J ComputAssist Tomogr,1998,22(1):15-24.
[145] S. IKEDA, H. TSURUKAMI, M. ITO, et al. Effect of Trabecular BoneContour on Ultimate Strength of Lumbar Vertebra After BilateralOvariectomy in Rats [J]. Bone,2001,28:625-633.
[146] Brudvik P, Rygh P. Root resorption beneath the main hya-linized zone.Eur J Orthod.1994;16:249–263.
[147] Day J, Ding M, Odgaard A, et al. Parallel Plate Model for TrabecularBone Exhibits Volume Fraction-Dependent Bias [J]. Bone,2000,27:715-720.
[148] Kohno T, Matsumoto Y, Kanno Z, et al. Experimental Tooth Movementunder Light Orthodontic Forces: Rates of Tooth Movement and Changes ofthe Periodontium. J Orthod,2002,29(2):129-135.
[149] Tomizuka R, Shimizu Y, Kanetaka H, et al. Histological evaluation ofthe effects of initially light and gradually increasing force on orthodontictooth movement. Angle Orthod,2007,77(3):410-416.
[150] T. Hildebrand, P. Rüegesegger. Structure Model Index–A NewMethod to Describe Remodeling of Trabecular Bone [J]. Bone,1996,supplement,19(3):143.
[151] X. E. Guo, C. H. Kim. Mechanical Consequence of Trabecular BoneLoss and Its Treatment: A Three-dimensional Model Simulation [J]. Bone,2002,30(2):404-411.
[152] Iegrand E, Chappard D, Pascaretti C, et al. Trabecular BoneMicroarchitecture, Bone Mineral Density, and Vertebral Fractures in MaleOsteoporosis. J Bone Miner Res,2000,15:13-19.
[153] Ronald JM, Robert S, James FF. The Effect of Altered BoneMetabolism on Orthodontic Tooth Movement. Am J R thod,1981;80(3):256-262.
[154]杨美祥,丁寅,徐如生,邹邦新.骨质疏松大鼠正畸牙齿的移动. JFourth Mil Med Univ,1999;20(7):628-629.
[155]庄丽,孟宪莹,白玉兴.正畸牙齿移动过程中牙槽骨的Micro-CT形态学研究.北京口腔医学,2009;17(4):181-183.