本文選題：生物活性　切入點(diǎn)：多肽　出處：《武漢理工大學(xué)》2012年碩士論文

【摘要】：本論文研究目的是制備一種具有生物活性的可促進(jìn)神經(jīng)修復(fù)的PLEOF水凝膠,并研究其性能,以解決合成高分子水凝膠缺乏細(xì)胞識(shí)別作用的問題,同時(shí)使PLEOF水凝膠具有誘導(dǎo)神經(jīng)再生的功能。 首先,采用丙交酯開環(huán)聚合法以辛酸亞錫為催化劑、一縮二乙二醇為共引發(fā)劑合成超低分子量的PLA,并以富馬酰氯連接超低分子量的PLA和PEG合成了PLEOF。1HNMR、 IR測(cè)試證實(shí)PLEOF大分子中成功的引入了不飽和的富馬酸酯基團(tuán),為水凝膠的合成提供了大分子單體。 采用固相多肽合成法合成YIGSR多肽交聯(lián)劑和末端含雙鍵的IKVAV多肽,紅外光譜和質(zhì)譜測(cè)試表明合成的YIGSR和IKVAV多肽與理論設(shè)計(jì)的結(jié)構(gòu)一致。利用骨髓間充質(zhì)干細(xì)胞完成IKVAV多肽促干細(xì)胞增殖實(shí)驗(yàn),確定當(dāng)IKVAV的濃度為0.1mmol/L時(shí),干細(xì)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水凝膠,由干細(xì)胞增殖實(shí)驗(yàn),確定IKVAV多肽含量, YIGSR多肽交聯(lián)劑的分子量較大,單位質(zhì)量的雙鍵濃度很低,單獨(dú)使用需要較大的投料量,不利于獲得具有恰當(dāng)組成的凝膠,因此兩種交聯(lián)劑混合使用。保持YIGSR的含量不變,改變BISAM的含量,得到Gell、Gel2、Gel3、Ge14、Ge15、Gel6、Gel7、Ge18、Ge19凝膠,其中Ge17因雙鍵濃度過低不成膠。IR表明凝膠中既有PLEOF分子成分,也有多肽成分；SEM表明Gell、Ge12、Ge13、Ge14、Ge15、Ge16、Ge18、Ge19凝膠均為多孔網(wǎng)絡(luò)結(jié)構(gòu)。Gell、Ge14孔徑最大,約為100um, Ge12、Ge15、Gel8的孔徑約為50umm,Gel3、Ge16、Ge19的孔徑最小,孔形狀不規(guī)則,Ge16、Ge19表面有較多的裂縫；測(cè)定凝膠溶脹性能,發(fā)現(xiàn)水凝膠的溶脹度主要受交聯(lián)密度影響,交聯(lián)密度越小,溶脹度越大。當(dāng)合成水凝膠的PLEOF大分子單體相同時(shí),凝膠的溶脹度大小關(guān)系為：GellGel2Ge13,Ge14Gel5Gel6,Gel8Gel9。PLEOF水凝膠能夠快速溶脹,這是凝膠的網(wǎng)絡(luò)骨架中親水性的PEG鏈段和水凝膠表面可以自由移動(dòng)的IKVAV多肽鏈段共同作用的結(jié)果；測(cè)定凝膠的降解性能,PLEOF水凝膠降解速率均很慢,30天內(nèi)Gell的質(zhì)量損失率為16.7%,Gel2為10.3%,Gel3為5.8%,Ge14為29.2%,Gel5為14.7%,Ge16為11.03%,Gel8為9.83%,Ge19為7.02%,其中Ge14的質(zhì)量損失率最大。水凝膠的交聯(lián)密度和PLEOF分子中PLA嵌段均對(duì)水凝膠的降解速率有影響,交聯(lián)密度越大,降解速率越小；PLEOF分子中PLA的嵌段比越大,水凝膠的降解速率越大。
[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，

本文編號(hào)：1704198