本文選題：N-組氨酸殼聚糖 + 聚乳酸��； 參考：《華僑大學(xué)》2014年博士論文

【摘要】：殼聚糖和聚乳酸是兩種性能優(yōu)良的生物材料，在組織工程和藥物釋放的應(yīng)用上均顯示其優(yōu)越性。組氨酸具有很好的pH響應(yīng)性，將組氨酸接枝到殼聚糖上制備N-組氨酸殼聚糖（NHCS），N-組氨酸殼聚糖保留了殼聚糖上的羥基和部分未取代的氨基以及新增加的具有pH響應(yīng)性的咪唑基團(tuán)，，保證了其具有良好的生物活性和pH響應(yīng)性，以期獲得一種綜合性能優(yōu)異的“復(fù)合型”組織工程材料（N-組氨酸殼聚糖支架、N-組氨酸殼聚糖/聚乳酸復(fù)合支架），可以進(jìn)一步拓寬殼聚糖、聚乳酸在生物醫(yī)學(xué)材料的應(yīng)用。本文主要研究了組氨酸改性殼聚糖及其與聚乳酸復(fù)合材料的制備，并著重研究這些新材料在仿生合成和蛋白分離上的應(yīng)用。 本文利用1-(3-二甲氨基丙基)-3-乙基碳二亞胺鹽酸鹽和N-羥基琥珀酰亞胺將組氨酸接枝到殼聚糖上，利用冷凍干燥法和濃縮干燥法分別制備N-組氨酸殼聚糖多孔支架（Ns）和N-組氨酸殼聚糖粉末（Np）；通過改變組氨酸/殼聚糖的摩爾比及殼聚糖分子量制得一系列不同取代度的N-組氨酸殼聚糖多孔支架（Ns）和N-組氨酸殼聚糖粉末（Np），通過FT-IR、1H NMR、EA、XRD、TGA和SEM等來表征，結(jié)果表明NHCS的取代度在3~11%之間，并且取代度受組氨酸的投加量和殼聚糖分子量的影響，組氨酸的投加量增大或殼聚糖分子量減小，取代度提高，支架孔徑增大。NHCS均可形成泡沫狀、海綿狀等多種多孔材料，孔尺寸在5~120μm之間，孔隙率均大于85%，NHCS支架可望滿足成纖維細(xì)胞、皮膚組織重建和骨組織工程的需要。 在冷凍誘導(dǎo)相分離制備N-組氨酸殼聚糖多孔支架（Ns）的基礎(chǔ)上進(jìn)行二次相分離，考察不同取代度的N-組氨酸殼聚糖多孔支架和不同的N-組氨酸殼聚糖/聚乳酸質(zhì)量之比等因素，制備一系列N-組氨酸殼聚糖/聚乳酸復(fù)合（NHCS/PLLA）支架，通過FT-IR、XRD、TGA和SEM等來表征N-組氨酸殼聚糖/聚乳酸復(fù)合支架，結(jié)果表明，NHCS/PLLA質(zhì)量之比減小，復(fù)合支架孔隙率減小，密度增大。復(fù)合支架材料的孔尺寸約在13~18μm，孔隙率均大于92%，不同組成的NHCS/PLLA支架的力學(xué)性能測試表明其抗壓強(qiáng)度和彈性模量分別在0.33~0.78MPa和1.75~5.28MPa之間，有望適用于軟骨組織工程支架。 利用濃縮干燥法所制備N-組氨酸殼聚糖粉末（Np）作為有機(jī)基質(zhì)，在模擬體液中仿生調(diào)控合成納米羥基磷灰石，探討組氨酸/殼聚糖摩爾比、殼聚糖分子量、鈣離子初始濃度、溫度和陳化時(shí)間等因素對NHCS調(diào)控合成羥基磷灰石的影響，并以不添加NHCS的水體系、模擬體液體系作對照，研究結(jié)果表明在不添加NHCS的水體系、模擬體液體系都能得到微米級的羥基磷灰石塊體。但在添加NHCS的模擬體液體系中可有效控制合成球形和梭狀的納米羥基磷灰石，以殼聚糖分子量為50kD、組氨酸與殼聚糖摩爾比為2:1所制備的NHCS（Np7）為有機(jī)基質(zhì)，NHCS投加量為0.01g、Ca2+離子初始濃度為0.01mol·L-1、反應(yīng)溫度為37.0℃、陳化時(shí)間為24h時(shí)調(diào)控效果最好，梭狀HAP長~200nm，寬~40nm，且含有少量碳羥基磷灰石，與自然骨成分相似。本研究還對NHCS不同投加量影響羥基磷灰石形成的機(jī)理作初步探討，為仿生合成羥基磷灰石及其骨骼修復(fù)等提供參考。 利用濃縮干燥法所制備N-組氨酸殼聚糖粉末（Np）作為有機(jī)基質(zhì)，在水體系中仿生調(diào)控合成碳酸鈣，探討不同的組氨酸/殼聚糖摩爾比、殼聚糖分子量、鈣離子初始濃度、pH值、溫度和陳化時(shí)間等因素對NHCS調(diào)控合成碳酸鈣的影響，并以不添加NHCS的水體系作對照。結(jié)果表明，在純水條件下，生成的產(chǎn)品為顆粒較大單一立方體的方解石。NHCS的添加能對合成的碳酸鈣晶型及形貌起到調(diào)控作用。NHCS在仿生合成碳酸鈣過程對體系pH具有響應(yīng)作用，體系pH不同，球形球霰石晶體的含量也不同，當(dāng)pH為6.5時(shí)，球霰石的含量最低為66.2%，當(dāng)pH遠(yuǎn)離6.5時(shí)，球霰石的含量可增加到93.7%。當(dāng)陳化時(shí)間的延長，球霰石的含量緩慢減小，24h后球霰石的含量為86.2%。此外，對體系pH值、陳化時(shí)間等因素影響球霰石形成的機(jī)理也作初步探討，為仿生合成其他生物礦物提供借鑒。 探究NHCS支架、NHCS/PLLA復(fù)合支架的吸附牛血清白蛋白（BSA）的性能，研究結(jié)果表明NHCS支架、NHCS/PLLA復(fù)合支架對牛血清白蛋白溶液吸附效果良好，吸附容量Qe在335.84~1048.64mg·g-1之間。單純NHCS支架中Ns10對BSA溶液的吸附能力最好，吸附容量Qe達(dá)820.90mg·g-1，而復(fù)合支架種以NPs3較佳，吸附容量Qe高達(dá)928.53mg·g-1。Ns10和NPs3可重復(fù)使用，重復(fù)吸附洗脫五次后的兩種支架對BSA的吸附容量只降低了1.00%左右，有望為BSA或其他蛋白的分離純化及回收利用提供新的載體，也有望作為組織工程用的支架材料。
[Abstract]:Chitosan and polylactide are two kinds of biological materials with excellent performance, showed its superiority in the application of tissue engineering and drug release. Histidine has good pH response, the histidine was grafted to chitosan preparation N- histidine chitosan (NHCS), N- histidine retained chitosan chitosan the hydroxyl and partially substituted amino and imidazole groups increased with pH response of, ensure its good biological activity and pH response, in order to obtain a kind of excellent performance composite materials for tissue engineering (N- histidine N- histidine chitosan scaffold, chitosan / polylactic acid composite), stent can further broaden chitosan, application of polylactic acid in biomedical materials. This paper mainly studies the histidine modified chitosan and polylactic acid composite material preparation, and focuses on the new material in bionic joint The application of the separation between the formation and the protein.
This paper uses 1- (3- two dimethylamino propyl) ethyl -3- carbon two imine hydrochloride and N- hydroxysuccinimide histidine grafted onto chitosan were prepared, N- histidine chitosan porous scaffolds by freeze-drying method and drying method (Ns) and N- histidine chitosan powder (Np); the change of histidine / chitosan the molar ratio and molecular weight of chitosan to prepare a series of different substituted N- histidine porous chitosan scaffolds of N- (Ns) and histidine chitosan powder (Np), by FT-IR, 1H NMR, EA, XRD, TGA and SEM to characterize the results show that the degree of substitution of NHCS in 3~11%, and the degree of substitution the histidine dosage and molecular weight of chitosan, the dosage of chitosan molecular weight increases or decreases the degree of substitution of histidine, improve stent diameter increases.NHCS can form a foam, sponge and other porous materials, pore size in 5~120 M The porosity is greater than 85%. NHCS scaffolds are expected to meet the needs of fibroblasts, skin tissue reconstruction and bone tissue engineering.
In the preparation of N- histidine chitosan porous scaffolds in frozen phase separation (Ns) on the basis of the two phase separation, the effects of different N- histidine chitosan porous scaffolds and the degree of substitution of histidine N- chitosan / poly lactic acid of different factors than the quality, the preparation of a series of N- histidine chitosan / polylactic acid composite (NHCS/PLLA) support, through FT-IR, XRD, TGA and SEM are used to characterize N- histidine chitosan / polylactic acid composite scaffolds, the results show that the NHCS/PLLA mass ratio decreases, the scaffold porosity decreases and the density increases. The pore size of composite scaffold materials in about 13~18 m, the porosity is greater than 92%, the mechanical performance test of NHCS/PLLA support different composition show that the compressive strength and elastic modulus were between 0.33~0.78MPa and 1.75~5.28MPa, is expected to apply to the scaffold for cartilage tissue engineering.
By using concentrated drying method prepared N- histidine chitosan powder (Np) was used as the organic matrix in the simulated body fluid regulation of biomimetic preparation of nano hydroxyapatite / chitosan on histidine, molar ratio, molecular weight of chitosan and calcium ion concentration, temperature and aging time and other factors on the synthesis of hydroxyapatite in the regulation of NHCS, and the do not add NHCS water system, simulated body fluid system as control. The results show that in NHCS was not added to the water system can be simulated body fluid system block hydroxyapatite micron. Nano hydroxyapatite in simulated body fluid, but the addition of NHCS can effectively control the synthesis of spherical and spindle shaped, with molecular weight of chitosan 50kD, histidine and chitosan molar ratio of 2:1 prepared by NHCS (Np7) as the organic matrix, the NHCS dosage of 0.01g, initial concentration of Ca2+ ions was 0.01mol L-1, the reaction temperature is 37 DEG C, Chen Time is the best control effect 24h, Clostridium HAP long ~200nm, wide ~40nm, which contains a small amount of carbon hydroxyapatite, similar to natural bone composition. The study of different NHCS dosage effect of hydroxyapatite formation mechanism are discussed, to provide reference for the synthesis of hydroxyapatite and its bionic bone repair.
By using concentrated drying method prepared N- histidine chitosan powder (Np) was used as the organic matrix in water system regulation biomimetic synthesis of calcium carbonate, explore different histidine / chitosan ratio, molecular weight of chitosan and calcium ion concentration, pH value, temperature and aging time and other factors on the regulation of NHCS carbonate synthesis calcium, and to add NHCS water system as control. The results showed that in pure water under the condition of generating products to add.NHCS calcite particles larger the single cube in biomimetic synthesis of calcium carbonate has effect on the pH response system of calcium carbonate crystal form and morphology play a regulatory role of.NHCS system. PH, the content of spherical vaterite crystals are different, when pH is 6.5, the lowest content of vaterite was 66.2%, when the pH is far from 6.5, the content of vaterite can be increased to 93.7%. when the aging time prolonged, the content of vaterite The content of 24h decreases slowly, vaterite is 86.2%. in addition, the system pH value, formation mechanism of vaterite aging time and other factors are discussed, to provide reference for the synthesis of other mineral biological bionic.
Study on NHCS NHCS/PLLA scaffolds, composite scaffolds for adsorption of bovine serum albumin (BSA) performance, the results show that the NHCS composite scaffold bracket, effect of NHCS/PLLA on bovine serum albumin adsorption, adsorption capacity of Qe between 335.84~1048.64mg g-1. NHCS Ns10 BSA to support simple solution adsorption ability best adsorption capacity of Qe reached 820.90mg - g-1 the composite scaffold with NPs3, better adsorption capacity of Qe reached 928.53mg - g-1.Ns10 and NPs3 can be used repeatedly, repeated adsorption and desorption adsorption capacity of two kinds of stents after five times of BSA was reduced by only 1% the left and right, purification and recycling is expected to provide a new carrier separation BSA or other protein, also is expected as the scaffold of tissue engineering.

【學(xué)位授予單位】：華僑大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R318.08

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 郭文豪;沈玉華;謝安建;桂東;裘靈光;;羧甲基葡聚糖/羥基磷灰石納米復(fù)合微粒的制備與表征[J];安徽大學(xué)學(xué)報(bào)(自然科學(xué)版);2007年04期

2 車蘭蘭;李衛(wèi)華;林勤保;;氨基酸分析檢測方法的研究進(jìn)展[J];氨基酸和生物資源;2011年02期

3 榮華;李巍;佟拉嘎;王英;;L-組氨酸陽離子型離子液體的實(shí)驗(yàn)研究[J];北京石油化工學(xué)院學(xué)報(bào);2012年01期

4 萬家瑰;畢鳳琴;;仿生超疏水涂層的制備及其性能[J];材料保護(hù);2010年07期

5 唐海雄;郭亞平;周玉;賈德昌;;以殼聚糖為添加劑制備單分散碳酸鈣微粒[J];稀有金屬材料與工程;2009年S2期

6 王少洪;王浩;侯朝霞;胡小丹;陸浩然;薛召露;牛廠磊;王彩;;Sol-Gel法合成納米羥基磷灰石及晶粒生長、結(jié)晶度的研究[J];稀有金屬材料與工程;2011年S1期

7 豐強(qiáng);閔思佳;張海萍;高欣;汪琦

本文編號：1739802