接枝YIGSR和IKVAV多肽的水凝胶的制备及性能研究

发布时间：2018-04-03 07:28

  本文选题：生物活性　切入点：多肽　出处：《武汉理工大学》2012年硕士论文

【摘要】：本论文研究目的是制备一种具有生物活性的可促进神经修复的PLEOF水凝胶,并研究其性能,以解决合成高分子水凝胶缺乏细胞识别作用的问题,同时使PLEOF水凝胶具有诱导神经再生的功能。 首先,采用丙交酯开环聚合法以辛酸亚锡为催化剂、一缩二乙二醇为共引发剂合成超低分子量的PLA,并以富马酰氯连接超低分子量的PLA和PEG合成了PLEOF。1HNMR、 IR测试证实PLEOF大分子中成功的引入了不饱和的富马酸酯基团,为水凝胶的合成提供了大分子单体。 采用固相多肽合成法合成YIGSR多肽交联剂和末端含双键的IKVAV多肽,红外光谱和质谱测试表明合成的YIGSR和IKVAV多肽与理论设计的结构一致。利用骨髓间充质干细胞完成IKVAV多肽促干细胞增殖实验,确定当IKVAV的浓度为0.1mmol/L时,干细胞增殖最好。 采用自由基共聚法合成表面接枝IKVAV和YIGSR多肽的PLEOF水凝胶,由干细胞增殖实验,确定IKVAV多肽含量, YIGSR多肽交联剂的分子量较大,单位质量的双键浓度很低,单独使用需要较大的投料量,不利于获得具有恰当组成的凝胶,因此两种交联剂混合使用。保持YIGSR的含量不变,改变BISAM的含量,得到Gell、Gel2、Gel3、Ge14、Ge15、Gel6、Gel7、Ge18、Ge19凝胶,其中Ge17因双键浓度过低不成胶。IR表明凝胶中既有PLEOF分子成分,也有多肽成分；SEM表明Gell、Ge12、Ge13、Ge14、Ge15、Ge16、Ge18、Ge19凝胶均为多孔网络结构。Gell、Ge14孔径最大,约为100um, Ge12、Ge15、Gel8的孔径约为50umm,Gel3、Ge16、Ge19的孔径最小,孔形状不规则,Ge16、Ge19表面有较多的裂缝；测定凝胶溶胀性能,发现水凝胶的溶胀度主要受交联密度影响,交联密度越小,溶胀度越大。当合成水凝胶的PLEOF大分子单体相同时,凝胶的溶胀度大小关系为：GellGel2Ge13,Ge14Gel5Gel6,Gel8Gel9。PLEOF水凝胶能够快速溶胀,这是凝胶的网络骨架中亲水性的PEG链段和水凝胶表面可以自由移动的IKVAV多肽链段共同作用的结果；测定凝胶的降解性能,PLEOF水凝胶降解速率均很慢,30天内Gell的质量损失率为16.7%,Gel2为10.3%,Gel3为5.8%,Ge14为29.2%,Gel5为14.7%,Ge16为11.03%,Gel8为9.83%,Ge19为7.02%,其中Ge14的质量损失率最大。水凝胶的交联密度和PLEOF分子中PLA嵌段均对水凝胶的降解速率有影响,交联密度越大,降解速率越小；PLEOF分子中PLA的嵌段比越大,水凝胶的降解速率越大。
[Abstract]:The purpose of this paper is to prepare a bioactive PLEOF hydrogel which can promote nerve repair and study its properties in order to solve the problem of cell recognition of synthetic polymer hydrogel.At the same time, PLEOF hydrogel can induce nerve regeneration.Firstly, stannous octanoate was used as catalyst by ring-opening polymerization of lactide.Very low molecular weight PLA was synthesized with diethylene glycol as co-initiator, and PLEOF.1HNMRs were synthesized by using fumaryl chloride to connect ultra-low molecular weight PLA and PEG. Ir results showed that unsaturated fumarate groups were successfully introduced into PLEOF macromolecules.It provides macromolecular monomer for the synthesis of hydrogel.YIGSR polypeptide crosslinker and IKVAV polypeptide with double bond at the end were synthesized by solid phase peptide synthesis. The IR and MS spectra showed that the synthesized YIGSR and IKVAV peptides were consistent with the theoretical design.Bone marrow mesenchymal stem cells (BMSCs) were used for IKVAV polypeptide to promote the proliferation of stem cells. It was found that when the concentration of IKVAV was 0.1mmol/L, the proliferation of stem cells was the best.PLEOF hydrogels grafted with IKVAV and YIGSR peptides were synthesized by free radical copolymerization. The content of IKVAV polypeptides was determined by stem cell proliferation experiment. The molecular weight of YIGSR polypeptide crosslinkers was large and the double bond concentration per unit mass was very low.A large amount of feed is needed to be used alone, which is not conducive to obtaining a gel with proper composition, so the two crosslinkers are mixed.淇濇寔YIGSR鐨勫惈閲忎笉鍙，

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