發(fā)布時(shí)間：2018-11-24 18:45

【摘要】：組織工程學(xué)的快速發(fā)展使醫(yī)學(xué)即將走出器官移植的范疇,步入制造組織和器官的新時(shí)代。組織工程支架材料是組織工程學(xué)實(shí)現(xiàn)臨床應(yīng)用的重要環(huán)節(jié),但是目前有關(guān)組織工程支架材料的制備仍存在溶劑殘留和生物降解特性不可控等問(wèn)題。 基于組織工程支架材料的要求,本文針對(duì)化學(xué)發(fā)泡制作技術(shù)存在的溶劑殘留的毒性問(wèn)題,采用無(wú)溶劑C02超臨界固態(tài)發(fā)泡技術(shù),在1-5MPa飽和壓力下制備了泡孔孔徑550-20μm的聚乳酸(PLA)支架材料,分析了泡孔孔徑與飽和壓力,發(fā)泡溫度,加壓時(shí)間等參數(shù)的對(duì)應(yīng)關(guān)系。基于熱重測(cè)量法提出了一種對(duì)組織工程PLA微孔支架材料進(jìn)行泡孔孔徑相關(guān)的熱分解動(dòng)力學(xué)特性評(píng)價(jià)和壽命估計(jì)的新方法。實(shí)驗(yàn)結(jié)果證明高飽和壓力條件下制備的PLA支架材料具有小泡孔孔徑和大泡孔密度；PLA原材料經(jīng)過(guò)發(fā)泡后熱穩(wěn)定性下降,降解時(shí)間縮短；在較低溫度下大泡孔孔徑支架材料具有較低的活化能和較差的熱穩(wěn)定性,其分解時(shí)間縮短到原材料的幾十分之一。 另外,針對(duì)閉孔支架材料的通透性差、細(xì)胞生長(zhǎng)代謝速度慢以及降解時(shí)間不可控等問(wèn)題,通過(guò)強(qiáng)功率脈沖超聲對(duì)PLA微孔支架材料進(jìn)行輻照打破泡孔壁來(lái)增強(qiáng)材料的通透性。首先從理論方面研究了超聲空化和超聲微射流技術(shù)以及PLA支架材料通透性增強(qiáng)原理,然后通過(guò)超聲輻射實(shí)驗(yàn)證明了隨著超聲輻射強(qiáng)度的提高,PLA支架材料泡孔孔壁破損增強(qiáng),泡孔連通性增強(qiáng)。另外研究了發(fā)泡材料中的聲傳播特性,建立了超聲插入取代特性檢測(cè)模型和實(shí)驗(yàn)系統(tǒng),對(duì)超聲輻射前后的發(fā)泡材料進(jìn)行了聲學(xué)測(cè)量,結(jié)果表明PLA支架材料的衰減系數(shù)和超聲輻射強(qiáng)度(通透性)呈現(xiàn)線性增大關(guān)系,但當(dāng)通透性足夠大時(shí),水能克服其表面張力進(jìn)入泡孔,材料的衰減系數(shù)迅速減小。 本研究針對(duì)組織器官對(duì)支架材料的泡孔孔徑和降解時(shí)間的要求,通過(guò)熱分解動(dòng)力學(xué)特性和聲學(xué)特性的測(cè)量來(lái)反映PLA微孔支架材料的形態(tài)結(jié)構(gòu),進(jìn)而優(yōu)化固態(tài)發(fā)泡制作參數(shù),為組織工程支架材料的精確設(shè)計(jì)及其降解特性的定量分析提供依據(jù),同時(shí)本研究提出的通透性超聲增強(qiáng)和超聲檢測(cè)新技術(shù),對(duì)組織工程支架材料的性能改善和檢測(cè)有著重要的應(yīng)用前景。
[Abstract]:With the rapid development of tissue engineering, medicine is about to step out of the field of organ transplantation and enter a new era of making tissues and organs. Tissue engineering scaffold is an important link in the clinical application of tissue engineering. However, the preparation of tissue engineering scaffolds still has some problems such as solvent residue and uncontrollable biodegradation characteristics. Based on the requirements of scaffold materials for tissue engineering, the solvent free C02 supercritical solid state foaming technology was used to solve the toxic problem of solvent residue in chemical foaming technology. Polylactic acid (PLA) scaffolds with a bubble pore diameter of 550-20 渭 m were prepared under the saturated pressure of 1-5MPa. The relationship between the pore size and the parameters such as saturation pressure, foaming temperature and pressure time was analyzed. Based on the thermogravimetric method, a new method for evaluating the thermal decomposition kinetics characteristics and life estimation of microporous PLA scaffolds in tissue engineering is proposed. The experimental results show that the PLA scaffolds prepared under high saturation pressure have small pore size and large pore density, the thermal stability of PLA raw materials decreases after foaming, and the degradation time is shortened. At lower temperatures, the macroporous scaffolds have low activation energy and poor thermal stability, and their decomposition time is reduced to a fraction of that of raw materials. In addition, aiming at the problems of poor permeability, slow cell growth and metabolism and uncontrollable degradation time, the permeability of PLA microporous scaffolds was enhanced by strong power pulse ultrasound irradiation to break the bubble wall. Firstly, the ultrasonic cavitation and ultrasonic microjet technology and the principle of enhancing the permeability of PLA scaffold materials are studied theoretically. Then, the ultrasonic radiation experiments show that the damage of the porous wall of PLA scaffold material increases with the increase of ultrasonic radiation intensity. The connectivity of bubble pores was enhanced. In addition, the acoustic propagation characteristics in the foamed materials are studied, and the testing model and experimental system of the ultrasonic insertion substitution characteristics are established, and the acoustic measurements of the foamed materials before and after ultrasonic radiation are carried out. The results show that the attenuation coefficient of PLA scaffold material increases linearly with the ultrasonic radiation intensity (permeability), but when the permeability is large enough, the water can overcome the surface tension and enter the bubble pore, and the attenuation coefficient of the material decreases rapidly. In this study, according to the requirements of tissue and organs on the pore size and degradation time of scaffolds, the morphology and structure of PLA microporous scaffolds were reflected by the measurement of thermal decomposition kinetics and acoustic characteristics, and then the parameters of solid foam fabrication were optimized. It provides the basis for accurate design and quantitative analysis of degradation characteristics of scaffold materials for tissue engineering. At the same time, a new technology of ultrasonic enhancement and ultrasonic detection of permeability is proposed in this study. It has an important application prospect for improving the properties and testing of scaffold materials for tissue engineering.
【學(xué)位授予單位】：南京師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08

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