本文選題：老齡 + 區(qū)域退化��； 參考：《吉林大學》2015年博士論文

【摘要】：通過了解老齡股骨頸骨折患者的股骨頭松質骨不同區(qū)域骨材料納觀表面形態(tài)和力學性能，探討股骨頭不同區(qū)域骨材料的老齡化過程和材料屬性，為降低臨床股骨頸骨折內固定術失敗率及探索老齡脆性骨折機理提供理論依據(jù)。同時觀測了骨折愈合過程中骨的顯微結構，骨質材料屬性分布的變化，及其與宏觀和微觀力學性能之間的關系，探討不同間歇方式的高頻率低載荷機械振動（LMHFV）對骨折愈合的影響，為臨床尋找合適的促進骨折愈合的物理方法提供理論基礎。 第一部分，選取女性股骨頸骨折后的股骨頭樣本10個，劃分為老齡（65-66歲）和高齡（85-95歲）兩個組別，每組5個樣本。將股骨頭沿冠狀面劃分為前（Ant）、中（Cen）、后（Pos）三個層面，每個層面劃分上（S）、中（C）、下（I）、內（M）、外（L）5個區(qū)域，分別采用原子力顯微鏡（AFM）和納米壓痕儀對每個區(qū)域骨小梁的橫向和縱向納觀表面形態(tài)和力學性能進行檢測。從整體、不同層面和不同區(qū)域三個角度探討老齡股骨頭骨小梁隨年齡的退化過程。結果表明，無論從股骨頭整體，還是不同層面、不同區(qū)域上看，均未發(fā)現(xiàn)骨小梁表面顆粒度和粗糙度隨年齡的顯著變化�？梢娊^經后女性骨小梁納觀形態(tài)不足以提供與骨折或骨質量下降相關的差異性。在老齡股骨頭整體骨小梁退化方向上，縱向顯著快于橫向；前面層退化程度較其他兩個層面偏快；在拉應力為主的區(qū)域（內，外側），其縱向力學性能的退化程度均高于其它3個區(qū)域，且縱向的退化均快于橫向。 第二部分，建立小尾寒羊的脛骨骨折模型，于骨折后4、8、12周分批處死，分別對傷側含骨痂脛骨部分和健側對應部分進行影像學評估和Micro-CT掃描，獲得顯微結構形態(tài)參數(shù)，建立傷側和健側顯微有限元模型，施加5%宏觀應變，計算得到宏觀及微觀力學參數(shù)。利用主元素分析法在骨質材料屬性分布和顯微結構參數(shù)中提取最能反應骨力學性能改變的主元素，并通過主元素與力學性能的線性回歸分析，建立他們之間的關系。結果表明，骨折模型建立4周時即可觀察到骨痂的生長，在8周時觀測到傷側彈性模量愈合百分比的增加，而到達12周后組織平均von Mises應力才出現(xiàn)大幅度增大。通過對顯微結構參數(shù)與骨質材料屬性分布的主元素分析得到了三個主元素，其累計貢獻率為87.60%，線性回歸結果表明，三個主元素線性擬合宏觀彈性模量和組織平均von Mises應力具備統(tǒng)計學意義（P0.05）。可見，，隨著骨折愈合進程的延續(xù)，含骨痂脛骨部分的力學性能明顯增加，基于Micro-CT的顯微有限元分析可以有效預測骨強度。骨折愈合過程中，骨質的材料屬性分布與顯微結構參數(shù)可以有效預測骨結構力學性能，反映骨折愈合進程中骨組織重建的過程，對進一步探索骨折愈合機理具有一定意義。 第三部分，選取大鼠35只，建立雙側脛骨橫行骨折模型，克氏針內固定。大鼠隨機分為5組，持續(xù)振動組（DL組，每天給予15分鐘LMHFV）；持續(xù)分次振動組（DLR組，每天施加LMHFV，每天3次，每次5分鐘，每2次振動實驗之間間隔4小時）；間歇7天振動組（VL7組，振動7天，休息7天，振動期間，每天1次LMHFV，每次15分鐘）；間歇7天分次振動組（VL7R組，振動7天，休息7天，振動期間分次振動方法同DLR組）和骨折對照組（FBC組）。大鼠骨折模型建立1周后開始實施振動實驗，振動頻率35Hz，加速度0.25g。實驗4周后，大鼠過麻處死，分別進行脛骨三點彎曲實驗、納米壓痕測試、原子力顯微鏡觀測，Micro-CT掃描、組織形態(tài)學觀察以及血清骨鈣素（OG）和抗酒石酸酸性磷酸酶（TRAP5b）檢測。結果表明：宏觀力學性能上，無論是破壞載荷還是彈性模量，DL組和DLR組都顯著高于FBC組（P0.05）；納觀力學性能上，DLR組在壓痕模量和硬度上均體現(xiàn)了最大值，且顯著高于FBC組（P0.05），同時DL組和VL7組硬度顯著高于FBC組（P0.05）。BMD分析顯示，DLR組和VL7組體現(xiàn)了較高的骨密度值，顯著高于FBC組（P0.05）。Micro-CT掃描獲得的微觀結構參數(shù)未發(fā)現(xiàn)各組間顯著差異。AFM檢測未觀測到顆粒度的明顯差異，而粗糙度DLR組最大，且顯著高于FBC組（P0.05）。血清生化檢測未發(fā)現(xiàn)各組間OG的顯著差異，F(xiàn)BC組TRAP5b顯著高于振動各組（P0.05）�？梢姡哳l率低載荷機械振動不僅在力學性能上（宏觀和納觀）體現(xiàn)了其對骨折愈合進程的促進作用，同時顯著影響了微觀骨密度（BMD）和骨材料在納觀空間排布（粗糙度），其中以持續(xù)并分次的振動方式（DLR組）對骨折愈合的促進作用最為明顯。可見在這一模式下，振動對骨折愈合的促進效果既達到了成骨累積，又使骨細胞力學敏感性得到了充分的恢復，具備很大的臨床應用潛力。
[Abstract]:The aging process and material properties of bone materials in different regions of the femoral head are discussed by understanding the surface morphology and mechanical properties of the bone materials in different regions of the femoral head of the aged femoral neck fracture. The theoretical basis for reducing the failure rate of internal fixation and exploring the mechanism of the aging brittle fracture is provided. The microstructure of bone, the change of the distribution of bone material properties and the relationship with the macroscopic and micromechanical properties were measured during the fracture healing process, and the effect of high frequency and low load mechanical vibration (LMHFV) on fracture healing was discussed in different intermittent ways, and the theoretical basis for finding a suitable physical method for promoting fracture healing was provided.
In the first part, 10 femoral head samples of femur neck fracture were selected and divided into two groups of aged (65-66 years old) and age (85-95 years old), each group was divided into 5 samples. The femoral head was divided into front (Ant), middle (Cen), and then (Pos) three layers, each layer was divided (S), middle (C), I, M, and outer (L) 5 regions, respectively. The transverse and longitudinal nanoscale surface morphology and mechanical properties of the bone trabecula in each region were detected by AFM and nanoindentation. The degradation process of the aged bone trabecular bone trabecula with the age was investigated from three angles, including the whole, the different layers and the different regions. There was no significant change in the grain size and roughness of the bone trabecular surface with age. It was found that the postmenopausal women's bone trabecular nanoscale morphology was not enough to provide the difference with the reduction of fracture or bone mass. In the direction of the degradation of the whole bone trabecula in the aged femoral head, the longitudinal direction was significantly faster than that in the transverse direction; the degree of degeneration in the front layer was more than the other two levels. Fast, in the tensile stress region (inside, outside), the longitudinal mechanical properties of the degradation degree is higher than the other 3 regions, and the longitudinal degradation is faster than the transverse.
In the second part, the model of tibial fracture of Small Tail Han sheep was established. After 4,8,12 weeks after the fracture, the images of the tibial part of the callus and the corresponding part of the injured side were evaluated by imaging and Micro-CT scanning respectively. The morphological parameters of the microstructures were obtained. The microscopic model of the injured side and the healthy side was established, and the macroscopic strain was applied to the macroscopic strain, and the macroscopic and the macroscopic strain was calculated. The principal element analysis method is used to extract the main elements which can reflect the changes of bone mechanical properties most in the properties of bone material properties and microstructure parameters. The relationship between the main elements and the mechanical properties is analyzed by linear regression analysis. The results show that the fracture model can be observed at 4 weeks. The percentage of the modulus of healing of the elastic modulus of the injured side increased at 8 weeks, and the average von Mises stress of the tissue increased greatly after 12 weeks. Three main elements were obtained by the analysis of the main elements of the microstructure parameters and the distribution of the properties of the bone material. The cumulative contribution rate was 87.60%. The linear regression results showed that three main elements lines were found. The macroscopic modulus of elasticity and the average von Mises stress of the tissue are statistically significant (P0.05). It is visible that the mechanical properties of the tibial part of the callus increase obviously with the continuation of the fracture healing process, and the bone strength based on the microscopic finite element analysis based on Micro-CT can be effectively predicted. The distribution of the material properties of bone in the process of bone fracture healing and the apparent distribution of bone material The microstructural parameters can effectively predict the mechanical properties of bone structure and reflect the process of bone tissue reconstruction in the process of fracture healing, which is of certain significance for further exploration of the mechanism of fracture healing.
The third part, 35 rats were selected to establish the bilateral tibial transverse fracture model and Kirschner pin internal fixation. The rats were randomly divided into 5 groups, the continuous vibration group (group DL, 15 minutes LMHFV per day); the continuous fractionation group (group DLR, 3 times a day, 5 minutes each day, 4 hours each 2 vibration experiments), and the intermittent 7 days vibration group (VL7 Group, vibration 7 days, rest 7 days, 1 times a day, 1 times a day, 15 minutes each time, 15 minutes each time, 7 days of intermittent vibration group (group VL7R, vibration 7 days, rest 7 days, vibration during the same group DLR group) and fracture control group (group FBC). Rats fracture model was established after the establishment of vibration experiment, vibration frequency 35Hz, acceleration 0.25g. Experiment 4 weeks later, Rats were killed by hemp, the three point bending test of tibia, nano indentation test, atomic force microscope observation, Micro-CT scan, histomorphology observation, Serum Osteocalcin (OG) and tartrate acid acid phosphatase (TRAP5b) were detected. The results showed that the macroscopic mechanical energy was on the damage load or modulus of elasticity, DL and DLR groups. Both significantly higher than the FBC group (P0.05), the maximum of the modulus and hardness of the DLR group was reflected in the mechanical properties of the DLR group, and was significantly higher than that in the FBC group (P0.05), and the hardness of the DL and VL7 groups was significantly higher than that of the FBC group (P0.05).BMD analysis, and the higher bone density was shown in the DLR group and the VL7 group. The microscopic structure parameters did not find significant differences between the.AFM detection and the significant difference in the granularity, while the roughness DLR group was the largest and significantly higher than that of the FBC group (P0.05). The serum biochemical test did not find the significant difference between the OG in each group, and the FBC group TRAP5b was significantly higher than that of the vibration group (P0.05). The high frequency and low load mechanical vibration is not only in the force of the mechanical vibration, but the mechanical vibration of the high frequency and low load is not only in the force. The learning performance (macroscopical and observational) reflects the promotion of fracture healing process, and it also significantly affects the microcosmic bone mineral density (BMD) and bone material in the nanoscale space (roughness), in which the continuous and fractionated mode of vibration (group DLR) promotes the healing of fracture most obviously. The promoting effect of the combination not only achieves the accumulation of bone, but also fully restores the mechanical sensitivity of bone cells, so it has great potential for clinical application.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R687.3

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