【作者】 牛旭锋；

【导师】 王远亮； 罗彦凤；

【作者基本信息】 重庆大学 ， 生物医学工程， 2006， 博士

【摘要】 “材料仿生修饰/工程”是第三代医用生物材料研究的热点。为了克服可降解医用生物材料聚乳酸的临床使用缺陷和满足其在生物医学工程领域的使用要求,本研究在以D,L-丙交酯（DL-LA）为原料,采用新型共引发体系合成高分子量聚（D,L-乳酸）（DL-PLA）的基础上,通过一系列化学改性来制备一种新型聚乳酸基仿生细胞外基质材料。采用多角度激光光散射仪（MALLS）、傅立叶变换红外光谱仪（FTIR）、核磁共振波谱仪（NMR）、X射线光电子能谱仪（XPS）、差示扫描量热计（DSC）、氨基酸分析仪（AAA）和常规化学分析方法等手段对所得材料进行结构表征和性能测试,并详细考察了其亲/疏水性、体外生物可降解性和生物相容性。主要研究内容和结论如下:⑴以D,L-丙交酯为原料,采用由Sn（Oct）2引发剂和自制的助引发剂共同组成的新型共引发体系来制备高分子量聚（D,L-乳酸）,重点考察了助引发剂在体系中的作用效果、助引发剂用量对产物分子量的影响以及共引发机理。①FTIR、¹³C NMR、¹H NMR和XPS的分析结果表明,采用该共引发体系能合成制备出DL-PLA材料;DSC分析显示合成得到的DL-PLA的玻璃化转变峰值温度为63.6℃。②MALLS的检测结果表明,在一定的浓度范围内,该共引发体系能明显加快聚合反应速率,缩短聚合反应时间,并且其用量也是影响产物分子量和分子量分布的重要因素。③回归分析的结果表明,与对照组不加助引发剂体系所得产物分子量的最大值仅为116,600相比,由S拟合得到的添加助引发剂体系的产物分子量极限值为153,300。因此,通过合理控制共引发体系中引发剂和助引发剂的用量,就可以得到高分子量的DL-PLA。⑵根据“材料整体仿生修饰”新思路,本研究将高分子量聚（D,L-乳酸）先用马来酸酐（MA）改性,再用脂肪族二胺（DA）改性,后用生物活性多肽（RGDS）改性,从而制备了一种新型仿生聚乳酸基质材料。其中,马来酸酐的引入主要是给材料提供高反应活性的酸酐键;二胺的引入主要是为了克服聚乳酸材料降解产物呈酸性的缺陷;而活性肽RGDS的引入则主要是为了赋予材料生物活性和给材料提供生物特异性。①FTIR、¹³C NMR和XPS的分析结果表明,在不影响DL-PLA材料主链结构的前提下,利用其分子结构中叔碳原子的自由基反应活性,在引发剂过氧化二苯甲酰（BPO）的作用下,能成功地将MA引入高分子量DL-PLA的分子骨架中,更多还原

【Abstract】 “Biomimetic modification or engineering of materials”is a new requirement of the third-generation biomaterials. Here, poly（D,L-lactic acid） （DL-PLA） with high molecular weight was prepared from D,L-lactide and modified in the bulk through a series of chemicals with the purpose of overcoming the drawbacks of DL-PLA in clinical use and building novel DL-PLA based biomimetic extracellular matrix materials. The characterization of the obtained polymers was by the means of multi-angle laser light scattering （MALLS）, fourier transform infrared spectrometry （FTIR）, nuclear magnetic resonance spectrometer （NMR）, X-ray photoelectron spectroscopy （XPS）, differential scanning calorimeter （DSC）, amino acid analyzer （AAA） and classical chemical analysis to explore the structures and the properties. Thereafter, surface wettability, biodegradation and biocompatibility of the synthetic materials were investigated. The main works and conclusions are included as follows:⑴Poly（D,L-lactic acid） with high molecular weight was synthesized by melt ring-opening polymerization of D,L-lactide using a novel co-initiating system. Then, an extensive investigation effort was expended in understanding the reacting mechanism, the effects of coinitiator and its dosage towards the molecular weight.①FTIR, ¹³C NMR, ¹H NMR and XPS analysis showed that DL-PLA was successfully prepared by using above-mentioned co-initiating system. Glass transition temperature of the synthetic polymer determined by DSC was 63.6℃.②The results of MALLS analysis indicated that the co-initiating system could accelerate the polymerization rate and shorten the reacting time. Moreover, decreasing the concentration of coinitiator in reacting system yielded polymer with higher molecular weight and narrower polydispersity.③Regression analysis revealed the maximal Mw of DL-PLA was only 116,600 by using single Sn（Oct）2 initiating system. However, sigmoidal fit discovered that the ultimate Mw of polymer prepared from co-initiating system was 153,300. Therefore, by controlling the initiator and coinitiator dosage into the optimum range, DL-PLA with maximum molecular weight was obtained.⑵Based on the design strategy of“bulk biomimetic modification or engineering of materials”, poly（D,L-lactic acid） was modified in the bulk with maleic anhydride （MA）, aliphatic diamine （DA） and bioactive peptide Arg-Gly-Asp-Ser （RGDS）,更多还原