本文選題：導(dǎo)電水凝膠　切入點(diǎn)：多孔支架　出處：《天津大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：本文通過“一步法”策略制備了兩種導(dǎo)電水凝膠(Conductive hydrogel,CH),由優(yōu)良導(dǎo)電性能的聚噻吩衍生物和具有良好生物相容性的天然高分子組成。綜合評價了CH溶脹性能、力學(xué)強(qiáng)度、電學(xué)性能及蛋白吸附特性。以棕色脂肪干細(xì)胞(BADSCs)為模型,系統(tǒng)研究了CH的組成對BADSCs粘附、增殖及向心肌細(xì)胞分化的調(diào)控作用及相關(guān)分子機(jī)制。聚噻吩基雙網(wǎng)絡(luò)導(dǎo)電水凝膠研制及性能評價:為了克服傳統(tǒng)兩步法制備導(dǎo)電水凝膠時組分不均勻的缺點(diǎn),以聚3-噻吩乙酸(PTAA)為導(dǎo)電剛性網(wǎng)絡(luò),光交聯(lián)明膠(MAAG)為柔性網(wǎng)絡(luò),在二甲基亞砜(DMSO)溶液中通過羰基二咪唑(CDI)交聯(lián)PTAA的羧基,同時采用光交聯(lián)的方法交聯(lián)MAAG,兩種反應(yīng)同時進(jìn)行且互不干涉,形成均一的雙網(wǎng)絡(luò)導(dǎo)電水凝膠(HEDN)。采用高分辨氫譜核磁共振(1HNMR)和傅里葉紅外光譜(FTIR)追蹤HEDN的形成,并系統(tǒng)研究了HEDN組成對其溶脹性能、力學(xué)強(qiáng)度和導(dǎo)電性能的調(diào)控作用。結(jié)果發(fā)現(xiàn)HEDN的理化性能可以通過調(diào)節(jié)PTAA網(wǎng)絡(luò)和MAAG網(wǎng)絡(luò)的比例實(shí)現(xiàn)調(diào)控。雙網(wǎng)絡(luò)水凝膠的壓縮力學(xué)強(qiáng)度在22.7 kPa到493.1 kPa之間,電導(dǎo)率約10-4 S·cm-1,與天然心肌組織的電導(dǎo)率相似。在此基礎(chǔ)上,將BADSCs種植在HEDN表面,在施加電刺激的作用下,通過原位熒光染色、免疫組織化學(xué)、免疫熒光、Western-Blotting等手段詳細(xì)研究了材料性能對BADSCs粘附、增殖以及向心肌細(xì)胞(MCs)分化的調(diào)控作用。結(jié)果發(fā)現(xiàn)HEDN可支持BADSCs的粘附與增殖,同時其行為與HEDN水凝膠的組成存在一定的相關(guān)性,例如:當(dāng)PTAA/MAAG質(zhì)量比例為1:1時,BADSCs表現(xiàn)出最好的增殖能力。更為重要的是HEDN水凝膠可調(diào)控BADSCs向心肌細(xì)胞分化的能力,PTAA網(wǎng)絡(luò)的引入可明顯增強(qiáng)心肌特異性蛋白(Cardiac troponin T和α-actinin)的表達(dá),同時促進(jìn)細(xì)胞間通訊。此外,電刺激可明顯增強(qiáng)BADSCs向心肌細(xì)胞分化的現(xiàn)象。聚噻吩基粒子增強(qiáng)型多孔支架研制及工程化心肌組織體外構(gòu)建:為了增強(qiáng)心肌組織工程支架材料的導(dǎo)電性和易加工性能,以聚乙烯二氧噻吩(PEDOT)海藻酸鈉為基材,通過一步法原位聚合、化學(xué)交聯(lián)方式在水相制備了聚乙烯二氧噻吩/海藻酸鈉水凝膠(PAEH),冷凍干燥后獲得多孔支架材料(PAMCS)。通過透射電鏡和掃描電鏡研究了支架中材料的組合方式和支架的形貌結(jié)構(gòu),同時系統(tǒng)研究了材料組成和結(jié)構(gòu)對PAMCS溶脹特性、降解性能、力學(xué)強(qiáng)度、電學(xué)性能和對蛋白的吸附能力的影響。結(jié)果表明,PAEH的儲能模量超過100 kPa,導(dǎo)電率大于10-2 S·cm-1,同時可通過調(diào)整PEDOT與海藻酸的比例控制其蛋白吸附能力。在此基礎(chǔ)上,以BADSCs為種子細(xì)胞,成功構(gòu)建了基于PAMCS支架的工程化心肌組織,系統(tǒng)的研究了BADSCs在PAMCS中的生物學(xué)行為,結(jié)果表明,相比單純海藻酸鈉支架,PEDOT的引入明顯增強(qiáng)支架的生物相容性,HE以及激光共聚焦結(jié)果表明BADSCs在PAMCS中分布均勻,生長良好。且PEDOT的引入可增強(qiáng)BADSCs向心肌細(xì)胞分化的能力,提高其cTnT和α-actinin蛋白的表達(dá)及Connexin 43的表達(dá)。
[Abstract]:This article through the "one-step" strategy has prepared two kinds of conductive hydrogel (Conductive hydrogel, CH), by the excellent conductive properties of polythiophene derivatives and natural polymers with good biocompatibility. The comprehensive evaluation of CH swelling properties, mechanical strength, electrical properties and protein adsorption. Brown adipose derived stem cells (BADSCs as a model system) on the CH of the composition of BADSCs adhesion, regulation of proliferation and differentiation into cardiomyocyte cells and the related molecular mechanism. Evaluation of polythiophene based conductive hydrogel preparation and properties of double network: in order to overcome the traditional two step preparation of conductive hydrogel component is not uniform, with poly (thiophene acetic acid 3- PTAA) for conducting rigid optical network (MAAG) is a flexible crosslinked gelatin network in two dimethyl sulfoxide (DMSO) solution by two carbonyl imidazole (CDI) cross-linked PTAA carboxyl, adopting the crosslinking of MA light AG, two kinds of reaction simultaneously without mutual interference, double network form a uniform conductive hydrogel (HEDN). Using high resolution nuclear magnetic resonance spectroscopy (1HNMR) and Fourier transform infrared spectroscopy (FTIR) to track the formation of HEDN, and study the HEDN composition on the swelling properties, mechanical strength and regulation of conductive properties the results showed that the regulation by adjusting the PTAA network and the MAAG ratio of the physical and chemical properties of HEDN can be compressed. The mechanical strength of double network hydrogel at 22.7 kPa to 493.1 kPa, the conductivity of about 10-4 S cm-1, and the natural cardiac tissue conductivity. On this basis, the BADSCs grown on the surface of HEDN and in the stimulation effect, by in situ fluorescence staining, immunohistochemistry, immunofluorescence, Western-Blotting and other means of a detailed study of the material properties on the BADSCs adhesion, proliferation and differentiation into cardiomyocytes (MCs) as the control . results showed that the proliferation and adhesion of HEDN can support BADSCs, while the composition of its behavior and HEDN hydrogel has certain relevance, for example: when the mass ratio of PTAA/MAAG to 1:1, BADSCs showed the best proliferation ability. What is more important is the HEDN hydrogel could regulate BADSCs differentiation into cardiomyocytes, the introduction of PTAA network could enhance the cardiac specific protein (Cardiac, troponin T and alpha -actinin) expression, while promoting intercellular communication. In addition, electrical stimulation can significantly enhance the cardiomyogenic differentiation of BADSCs phenomenon. Construction of polythiophene based particle enhanced development and tissue engineering scaffold in vitro: in order to enhance the myocardial tissue scaffold the conductivity and processability of polyethylene, two oxygen thiophene (PEDOT) sodium alginate as base material, through a one-step in situ polymerization, chemical crosslinking methods were prepared in aqueous polyethylene system Two oxygen thiophene / sodium alginate hydrogel (PAEH), obtained after freeze drying of porous scaffolds (PAMCS). The morphology by transmission electron microscope and scanning electron microscope study of the combination and stent materials, at the same time, the system of material composition and structure on PAMCS degradation properties, swelling properties, mechanical strength, electrical properties and effects the protein adsorption capacity. The results showed that the storage modulus of PAEH more than 100 kPa, the conductivity is greater than 10-2 S cm-1, at the same time can be controlled by adjusting the PEDOT protein and the ratio of alginate adsorption capacity. On this basis, using BADSCs as seed cells, successfully constructed myocardial tissue engineering based on the PAMCS scaffold. Systematic study on the biological behavior of BADSCs, in PAMCS the results show that compared with pure sodium alginate stent, the introduction of PEDOT significantly enhanced the compatibility of scaffold organisms, HE and confocal laser scanning results It indicates that BADSCs is well distributed and well distributed in PAMCS, and the introduction of PEDOT can enhance the ability of BADSCs to differentiate into cardiomyocytes, increase the expression of cTnT and -actinin and the expression of Connexin 43.

【學(xué)位授予單位】：天津大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R318.08;TQ427.26

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