EMPLGA的制备及多孔支架材料的研究

发布时间：2018-11-23 19:57

【摘要】：聚丙乙交酯(PLGA)是一种重要的生物医用材料，它具有良好的生物兼容性和降解周期可控等优点。但较弱的亲水性能和细胞粘附力，缺乏丰富的活性基团等限制了它在医学领域的应用。采用高分子共聚、接枝的方式对PLGA进行改性，改善它的亲水性和细胞亲和性、缓解降解过程中酸性物质的积累以及为材料的进一步仿生改性提供基础等，可以进一步拓展PLGA在生物医学领域上的应用。 本论文采用减压法，以辛酸亚锡(Sn(Oct)2)为催化剂，制备出了D,L-丙交酯和乙交酯单体。研究了不同提纯方法对两种单体纯度及产率的影响，，结果表明采用水洗-重结晶法对D,L-丙交酯进行提纯，六次重结晶后产物纯度可达99.47%。分别以异丙醇和乙酸乙酯作溶剂纯化乙交酯，得到产物的产率和纯度都偏低；采用异丙醇和乙酸乙酯配合使用的综合法能得到纯度达92.63%的乙交酯单体。 以D,L-丙交酯、乙交酯和马来酸酐为原料，采用开环聚合的方法制备了马来酸酐改性的聚丙乙交酯(MPLGA)，通过FT-IR和1HNMR分析证明马来酸酐已成功接入高分子骨架中。研究了催化剂用量、反应时间和反应温度对MPLGA分子量及分子量分布的影响。结果表明在催化剂用量为0.03%，反应温度140℃，反应时间36h时聚合得到的MPLGA重均分子量为5.3×104，分子量分布系数为1.51。利用MPLGA中酸酐键的N-酰化反应，制备了乙二胺改性的MPLGA产物EMPLGA，以进一步提高聚合物的亲水性和生物相容性。最后考察了聚合物改性前后的亲水性能的变化，研究发现EMPLGA的接触角远低于PLGA和MPLGA，说明EMPLGA有着优异的亲水性能，而酸酐键的引入使MPLGA的亲水性略弱于PLGA。 采用常温模压/粒子溶出法，制备了一系列多孔支架材料。考察了致孔剂粒径、致孔剂含量对支架材料的孔径、孔隙率、形貌及力学性能的影响。结果表明支架的孔隙率与致孔剂用量呈现出正比增长的关系；当致孔剂用量在90wt%时，支架的孔隙率可达81.86%，但支架的力学性能随致孔剂增加而呈下降趋势。支架的孔径随着致孔剂粒径增大而增大，因此可以通过控制致孔剂粒子的尺寸和质量百分比来控制多孔支架的孔结构。 研究了MPLGA和EMPLGA支架材料在PBS缓冲溶液中的降解行为。研究发现随着降解的进行两种材料的失重率、吸水率都在逐渐增大，而PBS溶液的pH值、支架的力学性能和分子量都呈下降趋势。其中MPLGA支架的失重率增加较快，EMPLGA中氨基的引入缓解了支架在降解过程中酸积累的问题，使材料降解环境保持在一个接近中性的状态，材料的失重率、力学性能都呈平稳下降趋势；而且EMPLGA中大量的亲水基团使材料的吸水率始终高于MPLGA。多孔支架的孔结构形态在降解5天后无明显变化；10天后在一些孔壁上腐蚀出少量的小孔；在25天时，已出现了一些较大的孔洞，且支架开始出现萎缩塌陷。
[Abstract]:Poly (glycolide) (PLGA) is an important biomedical material with good biocompatibility and controllable degradation cycle. However, its application in medical field is limited by its weak hydrophilicity, cell adhesion and lack of abundant active groups. PLGA was modified by polymeric copolymerization and grafting to improve its hydrophilicity and cellular affinity, to alleviate the accumulation of acidic substances in the degradation process and to provide the basis for further bionic modification of the materials. It can further expand the application of PLGA in biomedical field. In this paper, (Sn (Oct) _ 2 and L-lactide monomers were prepared by decompression method and stannous octanoate (Sn (Oct) _ 2) catalyst. The effects of different purification methods on the purity and yield of two monomers were studied. The results showed that the purity of DL- lactide was 99.47% after six recrystallization by water washing and recrystallization. Using isopropanol and ethyl acetate as solvent to purify glycolide, the yield and purity of the product were low, and the purity of glycolide monomer was 92.63% by using isopropanol and ethyl acetate. Poly (lactide) modified by maleic anhydride (MPLGA),) was prepared by ring-opening polymerization with DL- lactide, glycolide and maleic anhydride as raw materials. FT-IR and 1HNMR analysis showed that maleic anhydride had been successfully inserted into the polymer skeleton. The effects of the amount of catalyst, reaction time and reaction temperature on the molecular weight and molecular weight distribution of MPLGA were studied. The results show that when the amount of catalyst is 0.03, the reaction temperature is 140 鈩

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