明胶接枝改性及其复合水凝胶支架的研究

发布时间：2018-03-25 06:23

  本文选题：明胶交联　切入点：聚(N-异丙基丙烯酰胺)　出处：《北京化工大学》2014年硕士论文

【摘要】：明胶是胶原蛋白的水解产物,具有良好的生物活性,且在人体内可由多种蛋白酶进行降解,因此被广泛应用于组织工程支架材料、药物载体等领域,而作为水凝胶进行非承重骨的临界骨缺损修复,以促进骨组织的再生,更是其中一个研究热点。由于明胶亲水性很好,由其制备的水凝胶支架必须要通过交联来降低支架的溶解或溶胀,从而维持支架结构稳定性通常采用化学交联剂对明胶支架进行交联,所得水凝胶虽然有很好的稳定性,但小分子化学试剂的毒性会对细胞或所负载的生物活性物质造成不利影响,并且交联剂在材料中的扩散会引起支架由表及里交联程度不一致。而物理交联的方法可以避免这些问题的发生。在明胶侧链接枝高分子,利用侧链之间发生的的物理作用对明胶起到交联效果被认为是一种有效的交联方式。 本论文分别向明胶侧链引入了两种合成高分子链段,分别研究了这两种高分子对于明胶的交联作用。首先利用明胶侧链的游离氨基,将其与α-溴代异丁酰溴(BIBB)进行反应生成原子转移自由基聚合反应(ATRP)的引发剂——带有溴官能团的明胶大分子(Gel-Br)。当BIBB与明胶的原料比不同时可制备出不同溴取代程度的引发剂,接下来分别进行了两种接枝聚合物的制备及表征工作： (1)明胶接枝聚(N-异丙基丙烯酰胺)(Gel-g-PNIPAAm),利用NIPAAm的温度响应性——在高于LCST的环境下会发生相转变,从而起到交联明胶的作用。 采用“Graft-from"的方式将NIPAAm单体聚合到明胶分子上,调节反应得到不同接枝密度、不同链长的Gel-g-PNIPAAm共聚物,并对共聚物结构进行表征；上述接枝共聚物水溶液具有显著的温敏性,在37℃下迅速转变为不可流动的水凝胶态；且可通过改变PNIPAAn的接枝率和接枝量可调节共聚物的LCST和37℃下的热致相变行为。通过体外细胞生物学实验以及体内动物学表征证实该水凝胶具有良好的生物相容性,可以作为细胞载体用于非承重骨缺损的修复。 (2)明胶分别接枝左旋聚乳酸(Gel-g-PLLA)和右旋聚乳酸(Gel-g-PDLA),利用两种不同旋光性的聚乳酸在同一体系中可以发生立构复合作用,分子链间通过氢键作用规整排列,从而促进明胶的交联,也是一种物理交联明胶的方法。 首先制备得到两种构象的单端羟基聚乳酸,通过改性将羟基转化为碳碳双键；然后分别由Gel-Br引发进行ATRP聚合,得到Gel-g-PLLA和Gel-g-PDLA;通过调节聚乳酸的接枝密度、链段长度,得到具有不同性能的接枝聚合物；将两种接枝聚合物在同一体系中混合,浇铸成膜,差热扫描量热仪测试(DSC)和X射线衍射能谱分析(XRD)证实有立构复合物的生成。初步证实该方法可以用于交联明胶。
[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 伪 -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，

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