本文選題：心肌組織工程　切入點：纖維束　出處：《清華大學(xué)》2012年碩士論文

【摘要】：本論文在分析天然心肌組成與結(jié)構(gòu)特點的基礎(chǔ)上，依照組織工程的仿生設(shè)計原則與“自下而上”組元化構(gòu)建思路，提出了以含心肌細(xì)胞水凝膠纖維絲有序組裝構(gòu)建組織工程心肌纖維束的工藝路線。論文系統(tǒng)地研究了與組織工程心肌纖維束的設(shè)計、成形、應(yīng)用相關(guān)的科學(xué)與技術(shù)問題，主要工作包括：從材料和結(jié)構(gòu)兩個方面進(jìn)行了纖維束結(jié)構(gòu)體的設(shè)計與分析；設(shè)計開發(fā)了水凝膠纖維絲的成形工藝和裝置，完成了工藝原理分析和工藝參數(shù)研究；對構(gòu)建的纖維束結(jié)構(gòu)體，對其進(jìn)行了力學(xué)性能的表征與評價；將工藝應(yīng)用于環(huán)狀組織工程心肌纖維束的構(gòu)建，并進(jìn)行初步的生物學(xué)評價。 論文取得的主要結(jié)果包括：（1）模仿天然心肌組織的組成、結(jié)構(gòu)及其內(nèi)部微環(huán)境，設(shè)計了組織工程心肌纖維束，由含心肌細(xì)胞水凝膠纖維絲有序組裝構(gòu)建而成；纖維絲采用“海藻酸鈉-纖維蛋白-Matrigel”仿生材料體系，平均直徑為150~250μm，以滿足氧在水凝膠材料中的擴(kuò)散距離限制；纖維絲之間的間隙間接構(gòu)成了微通道網(wǎng)絡(luò)，通過FLUENT軟件和理論計算對微通道灌流流場和供氧狀態(tài)進(jìn)行了分析與評價，得出了能在整個結(jié)構(gòu)體內(nèi)部營造富氧環(huán)境的有益結(jié)論；（2）設(shè)計開發(fā)了基于海藻酸鈉的攪拌纏繞濕法成絲工藝，實現(xiàn)了纖維絲的連續(xù)穩(wěn)定成形，并利用磁轉(zhuǎn)子攪拌實現(xiàn)了纖維絲的纏繞有序收集，成功制備了纖細(xì)均勻的纖維絲和細(xì)胞復(fù)合的纖維絲，并以此為組裝單元實現(xiàn)了多種纖維束結(jié)構(gòu)體的構(gòu)建；（3）深入研究了工藝參數(shù)對纖維絲成形質(zhì)量的影響關(guān)系，根據(jù)實驗結(jié)果確定了成形參數(shù)方案，同時對纖維絲組成的纖維束結(jié)構(gòu)體的力學(xué)性能進(jìn)行了研究，為滿足后續(xù)的組織工程體外培養(yǎng)和訓(xùn)練的要求提供了依據(jù)；（4）完成了環(huán)狀組織工程心肌纖維束的成形構(gòu)建、體外培養(yǎng)和力學(xué)拉伸訓(xùn)練，對其進(jìn)行了生物學(xué)評價，實驗結(jié)果表明：纖維絲的材料體系具有良好的生物相容性；結(jié)合含鈣培養(yǎng)環(huán)境和力學(xué)拉伸訓(xùn)練，纖維束結(jié)構(gòu)能長時間穩(wěn)定保持，局部的心肌細(xì)胞實現(xiàn)了定向排布與連接，形成了具有方向性的纖維狀類組織形態(tài)。
[Abstract]:On the basis of analyzing the composition and structural characteristics of natural myocardium, according to the bionic design principle of tissue engineering and the idea of "bottom-up" component construction, In this paper, the process of constructing tissue engineered myocardial fiber bundle by orderly assembly of hydrogel fiber filament containing cardiomyocytes is presented. The scientific and technical problems related to the design, forming and application of tissue engineering myocardial fiber bundle are systematically studied in this paper. The main work includes: the design and analysis of fiber bundle structure from two aspects of material and structure, the design and development of forming process and equipment of hydrogel fiber filament, the process principle analysis and process parameter research; The mechanical properties of the fiber bundle were characterized and evaluated, and the process was applied to the construction of annular tissue engineering myocardial fiber bundle, and the preliminary biological evaluation was carried out. The main results obtained in this paper are as follows: (1) mimicking the composition, structure and internal microenvironment of natural myocardial tissue, a tissue engineered myocardial fiber bundle was designed and constructed from the ordered assembly of hydrogel filament containing cardiomyocytes. The fiber is made of "alginate-fibrin-Matrigel" biomimetic material system, with an average diameter of 150 ~ 250 渭 m, to satisfy the limit of oxygen diffusion distance in hydrogel materials, and the gap between fibers indirectly forms a microchannel network. The flow field and oxygen supply state of microchannel were analyzed and evaluated by FLUENT software and theoretical calculation. It is concluded that the oxygen-enriched environment can be created in the whole structure. (2) A wet spinning process based on sodium alginate is designed and developed to realize the continuous and stable forming of the filament. The winding and orderly collection of the filament was realized by magnetic rotor stirring, and the fine and uniform filament and the cell-composite filament were successfully prepared. The influence of process parameters on fiber forming quality is studied deeply, and the forming parameter scheme is determined according to the experimental results. At the same time, the mechanical properties of the fiber bundle structure were studied, which provided the basis for the in vitro culture and training of the subsequent tissue engineering, and completed the forming and construction of the annular tissue engineering myocardial fiber bundle. The biological evaluation of in vitro culture and mechanical stretching training was carried out. The experimental results showed that the material system of fiber had good biocompatibility, combined with calcium containing culture environment and mechanical stretching training, The fibrous bundle structure can be kept stable for a long time, and the local cardiac myocytes can be arranged and connected in a directional way, forming a directional fibrous tissue shape.
【學(xué)位授予單位】：清華大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R318.11

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