本文選題：明膠交聯(lián)　切入點(diǎn)：聚(N-異丙基丙烯酰胺)　出處：《北京化工大學(xué)》2014年碩士論文

【摘要】：明膠是膠原蛋白的水解產(chǎn)物,具有良好的生物活性,且在人體內(nèi)可由多種蛋白酶進(jìn)行降解,因此被廣泛應(yīng)用于組織工程支架材料、藥物載體等領(lǐng)域,而作為水凝膠進(jìn)行非承重骨的臨界骨缺損修復(fù),以促進(jìn)骨組織的再生,更是其中一個(gè)研究熱點(diǎn)。由于明膠親水性很好,由其制備的水凝膠支架必須要通過(guò)交聯(lián)來(lái)降低支架的溶解或溶脹,從而維持支架結(jié)構(gòu)穩(wěn)定性通常采用化學(xué)交聯(lián)劑對(duì)明膠支架進(jìn)行交聯(lián),所得水凝膠雖然有很好的穩(wěn)定性,但小分子化學(xué)試劑的毒性會(huì)對(duì)細(xì)胞或所負(fù)載的生物活性物質(zhì)造成不利影響,并且交聯(lián)劑在材料中的擴(kuò)散會(huì)引起支架由表及里交聯(lián)程度不一致。而物理交聯(lián)的方法可以避免這些問(wèn)題的發(fā)生。在明膠側(cè)鏈接枝高分子,利用側(cè)鏈之間發(fā)生的的物理作用對(duì)明膠起到交聯(lián)效果被認(rèn)為是一種有效的交聯(lián)方式。 本論文分別向明膠側(cè)鏈引入了兩種合成高分子鏈段,分別研究了這兩種高分子對(duì)于明膠的交聯(lián)作用。首先利用明膠側(cè)鏈的游離氨基,將其與α-溴代異丁酰溴(BIBB)進(jìn)行反應(yīng)生成原子轉(zhuǎn)移自由基聚合反應(yīng)(ATRP)的引發(fā)劑——帶有溴官能團(tuán)的明膠大分子(Gel-Br)。當(dāng)BIBB與明膠的原料比不同時(shí)可制備出不同溴取代程度的引發(fā)劑,接下來(lái)分別進(jìn)行了兩種接枝聚合物的制備及表征工作： (1)明膠接枝聚(N-異丙基丙烯酰胺)(Gel-g-PNIPAAm),利用NIPAAm的溫度響應(yīng)性——在高于LCST的環(huán)境下會(huì)發(fā)生相轉(zhuǎn)變,從而起到交聯(lián)明膠的作用。 采用“Graft-from"的方式將NIPAAm單體聚合到明膠分子上,調(diào)節(jié)反應(yīng)得到不同接枝密度、不同鏈長(zhǎng)的Gel-g-PNIPAAm共聚物,并對(duì)共聚物結(jié)構(gòu)進(jìn)行表征；上述接枝共聚物水溶液具有顯著的溫敏性,在37℃下迅速轉(zhuǎn)變?yōu)椴豢闪鲃?dòng)的水凝膠態(tài)；且可通過(guò)改變PNIPAAn的接枝率和接枝量可調(diào)節(jié)共聚物的LCST和37℃下的熱致相變行為。通過(guò)體外細(xì)胞生物學(xué)實(shí)驗(yàn)以及體內(nèi)動(dòng)物學(xué)表征證實(shí)該水凝膠具有良好的生物相容性,可以作為細(xì)胞載體用于非承重骨缺損的修復(fù)。 (2)明膠分別接枝左旋聚乳酸(Gel-g-PLLA)和右旋聚乳酸(Gel-g-PDLA),利用兩種不同旋光性的聚乳酸在同一體系中可以發(fā)生立構(gòu)復(fù)合作用,分子鏈間通過(guò)氫鍵作用規(guī)整排列,從而促進(jìn)明膠的交聯(lián),也是一種物理交聯(lián)明膠的方法。 首先制備得到兩種構(gòu)象的單端羥基聚乳酸,通過(guò)改性將羥基轉(zhuǎn)化為碳碳雙鍵；然后分別由Gel-Br引發(fā)進(jìn)行ATRP聚合,得到Gel-g-PLLA和Gel-g-PDLA;通過(guò)調(diào)節(jié)聚乳酸的接枝密度、鏈段長(zhǎng)度,得到具有不同性能的接枝聚合物；將兩種接枝聚合物在同一體系中混合,澆鑄成膜,差熱掃描量熱儀測(cè)試(DSC)和X射線衍射能譜分析(XRD)證實(shí)有立構(gòu)復(fù)合物的生成。初步證實(shí)該方法可以用于交聯(lián)明膠。
[Abstract]:Gelatin is a hydrolytic product of collagen, which has good bioactivity and can be degraded by many proteases in human body. Therefore, it is widely used in tissue engineering scaffold materials, drug carriers and other fields. As a hydrogel to repair the critical bone defect of non-load-bearing bone to promote bone tissue regeneration, it is one of the research hotspots. Because of the good hydrophilicity of gelatin, The hydrogel scaffolds prepared by the hydrogels must be crosslinked to reduce the dissolution or swelling of the scaffolds, so as to maintain the stability of the scaffolds. Chemical crosslinking agents are usually used to cross-link the gelatin scaffolds, and the resulting hydrogels have good stability. But the toxicity of small molecular chemicals can adversely affect cells or the bioactive substances loaded, And the diffusion of crosslinking agent in the material will lead to the inconsistency of crosslinking degree from outside to inside of the scaffold. The physical crosslinking method can avoid these problems. The physical interaction between the side chains is considered to be an effective crosslinking method for gelatin. In this paper, two kinds of synthetic polymer chains were introduced to the side chain of gelatin respectively, and the crosslinking of the two polymers to gelatin was studied. Firstly, the free amino group of the side chain of gelatin was used. The initiator of atom transfer radical polymerization (ATRP) was synthesized by the reaction of 偽 -bromoisobutylol bromobutylbromobutylbromide (BIBB) with the gelatin macromolecule with bromine functional groups. When the ratio of BIBB to gelatin was different, the initiators with different bromine substitutions could be prepared. Then two kinds of grafted polymers were prepared and characterized. 1) Gel-g-PNIPAAmam, which is grafted by gelatin, can change the phase of Gel-g-PNIPAAmN when the temperature response of NIPAAm is higher than that of LCST, and thus play the role of crosslinking gelatin. The NIPAAm monomer was polymerized onto gelatin molecule by "Graft-from", and the graft density and chain length of Gel-g-PNIPAAm copolymer were obtained by adjusting the reaction, and the copolymer structure was characterized. At 37 鈩，

本文編號(hào)：1661925