在精密的人體中，神經系統扮演著重要的角色，一旦神經系統因為外傷或病變而受損，便會影響病人的日常生活，造成患者家人與社會的負擔。隨著時代進步，意外傷害與一些文明病例不斷增加，神經傷害與病變的發生率亦愈趨嚴重，導致身體的運動與感覺機能的喪失。近年來，由於微機電製程的進步及動物實驗技術的成熟，促進了神經性義肢的發展。神經性義肢的概念是經由人造的感測器與刺激器，取代原本無法傳遞訊號的病變或損傷神經，恢復患者失去的運動功能。其中作為人機介面的神經電極極為關鍵，因為周邊神經由不同的結締組織所構成，類似其他生命軟組織，屬於黏彈性材料。瞭解周邊神經組織與細胞力學特性，可能有助於神經義肢之神經電極的設計，以及神經修復與再生的研究。
本研究從生物力學特性的角度，藉由動物實驗研究正常與糖尿病神經病變白鼠坐骨神經的機械性質，以自行開發之動態量測系統，設計離體與在位實驗，對坐骨神經進行橫向壓縮測試，同時分析神經組織的力學特性與量測神經內微循環的變化，分別以彈性與黏彈性模型建立神經組織的一維構成方程式。為了改善以往在建構生命材料之類線性黏彈模型時，需要耗費過久的參數估測時間與複雜的分析步驟，本研究提出快速迴旋積分法，以此發展估測類線性黏彈模型參數的新方法，可以準確地估測模型參數與有效地降低計算時間。另一方面，在動物實驗後取得神經組織的橫切面影像，經由影像處理與實驗所得之材料特性，建構神經組織的二維有限元素模型，分別以片段線彈性與超彈性材料模型分析神經的力學行為，應用最佳化程序以逆向有限元素分析決定神經內三層組織之應力應變關係，最後將力學實驗與分析方法應用至糖尿病神經病變的病程對神經組織機械性質的影響，與類神經細胞力學特性之研究，探討PC-12細胞本體與軸突的機械性質，比較以彈性模型與黏彈性模型在描述細胞力學特性上的差異。
本研究所開發之環形壓縮系統，成功地完成白鼠坐骨神經組織的在位壓縮實驗與受壓下神經內血流量的量測。橫向外觀楊氏係數的估測結果顯示糖尿病變神經的機械性質在病程上有先硬後軟的趨勢。在微循環變化的量測方面，糖尿病變神經在受橫向壓力下，神經內血流量會比正常神經先下降，之後可能受到組織硬化的影響，血流量下降程度反而比正常神經低。根據類線性黏彈模型參數的估測結果，顯示糖尿病變神經具有較弱的黏性響應與需要較長時間達到穩定的鬆弛狀態。本研究提出之快速迴旋積分法在估測類線性黏彈模型的參數時，可以比時域迴旋積分有效降低49％的計算時間，而且不會增加模型預測值與實驗結果的誤差。另外本研究以逆向有限元素分析分別估測出正常與糖尿病白鼠神經組織三層結構之增量楊氏係數，結果顯示神經束膜為主要應力承受區，其次為神經外膜，最後為神經內膜，代表神經外膜和神經束膜有保護作用，而此二維有限元素模型，不但能分析神經各分層的材料特性，也可以用來模擬神經病變組織各層力學特性的變化。類神經細胞的研究結果指出以類線性黏彈模型估測出的楊氏係數比較不會受到壓印速率的影響，PC-12細胞本體的楊氏係數呈現由中央區向外遞增的趨勢，以邊緣區最大，過渡區次之，中央區最小，軸突部分各區域則無明顯差異。
本研究發展之力學分析與模型建立的方法可應用至其他生命軟組織的測試，並將相關生命材料的機械性質資訊建立資料庫，依此評估組織與細胞特性的變化與病變的影響，提供臨床上相關研究的理論基礎。

The nervous system plays an important role in the human body such that, nerve injuries due to trauma or dieases can affect a patient’s daily life and increase the burden of the family and society. Incidence of nerve injuries and neurological disorders such as diabetes mellitus are increasing in modern society like Taiwan, resulting in the loss of motor and sensory functions on the victims. Recent advancement in the MEMS technology and the neuroscience enhance the development of neural prostheses for replacing the damaged nerves whose signal transmission function is impeded. With a neural prosthesis, signals can be transmitted through artificial sensing and stimulating electrodes to restore the lost motor function. Nerve electrodes are critical in neural protheses as peripheral nerves are constituted by very soft connective tissues. These tissues, similar to other biological soft tissues, are composed of viscoelastic materials. Understanding mechanical properties of peripheral nerve tissues and cells may help better design of electrodes for neural prosthesis and understanding nerve repair and regeneration mechanisms.
In this dissertation, the mechanical characteristics of sciatic nerves of normal and diabetic rats were investigated through animal experiments. A custom-designed dynamic testing apparatus was used to conduct the in vitro and in situ compression experiments on the sciatic nerve of rats, and to analyze the transverse biomechanical properties as well as to measure the endoneurial microcirculation of nerve tissues. An elastic model and a viscoelastic model were adopted to derive one-dimensional constitutive equations for the sciatic nerves. To improve the computational efficiency and to simplify procedures for building the quasi-linear viscoelastic (QLV) model of biomaterials, a new fast convolution method was developed. Furthermore, a two-dimensional finite element model was established for the nerve tissues and mechanical properties of each layer were derived by comparing simulation and in situ experimental results. The geometry of the three layers of the nerve was acquired by processing the cross-section of a nerve image. A piecewise linear elastic model and a hyperelastic model were employed to describe the mechanical properties of the nerve tissues. The inverse finite element analysis was used to identify the stress-strain relationship of the three layers of nerve. The time-course effects of diabetic neuropathy on biomechanical properties of the nerve and biomechanics of PC-12 cells were investigated.
The in situ transverse apparent Young’s modulus of sciatic nerves in normal and diabetic rats was obtained respectively using the compression apparatus. The results suggested that the sciatic nerve was stiffer and became softer as the disease progressed. The pressure threshold that blood perfusion started to decrease in diabetic rats was smaller than in normal controls. Furthermore, when the blood perfusion reached the steady state, there was less reduction of blood perfusion in the diabetic rats than in the normal rats which might due to the stiffer nerves. From the estimated parameters of the QLV model, the diabetic nerves had a smaller amplitude of viscous response and a longer relaxation period to reach equilibrium. The computation time was cut down 49% by using the newly developed fast convolution method in this study without increasing the estimation error. The results of incremental Young’s moduli for the three nerve layers in normal and diabetic rats indicated that the perineurium was the main stress bearing layer, followed by epineurium and endoneurium demonstrating the protective function of epineurium and perineurium. The two-dimensional finite element model can be used to analyze the material properties of each nerve layer, and simulate the changes of mechanical properties of neuropathic tissues. The results of PC-12 cells revealed that the Young’s modulus estimated by the QLV model was less affected by indenting rates than that estimated by the modified Hertzian model or the Kelvin model. The Young’s modulus of PC-12 cell soma was region-dependent in which the edge had the highest Young’s modulus while the central region had the lowest. The Young’s moduli were nearly identical for the three regions of the axon.
The methods of biomechanical analysis and model construction developed in this dissertation may be applied to other soft tissues and cells. The mechanical properties of soft tissues may be used to construct a database for assessing the changes of mechanical characteristics of tissue in regeneration and the effects of pathology. In addition, this technique and methodology will serve as an impetus for other clinical applications in the future.

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