再生丝素可注射原位水凝胶的制备与表征

发布时间：2019-01-21 16:14

【摘要】：可注射原位丝素（SF）水凝胶具有手术创伤微小的优点，在各种生物材料中具有潜在的应用优势。作为一种理想的可注射性原位水凝胶材料，自身需能够快速凝胶化以满足在体内注射后凝胶能够立即成型的需要。本文研究了两类小分子的表面活性剂，即十二烷基硫酸钠（SDS）、十二烷基醚硫酸钠（AES）等硫酸酯盐类阴离子表面活性剂和季铵盐类阳离子表面活性剂对家蚕丝素凝胶化、丝素凝胶结构和性能的影响，并探讨了相应的丝素原位凝胶化机理。硫酸酯盐类阴离子表面活性剂能够缩短丝素凝胶化的时间，且其对丝素凝胶化的促进程度与自身疏水烃链长度有着直接的关系，烃链较短（㩳8）时，对丝素凝胶化无明显的促进作用，而随着烃链的延长，相应丝素的胶凝速度有增加的趋势。详细研究了SDS引发丝素快速凝胶化的机制，并对硫酸盐类阴离子表面活性剂-丝素复合水凝胶的结构和力学、降解、体外释药等性能进行了表征。其中释药结果表明，，SDS、AES促发形成的(SDS/SF、AES/SF)凝胶对阿霉素这种模型药物的体外释放呈现出，前期（1-10天）释放量较大且持续时间较长，而后期（10-38天）释放缓慢且速率较为恒定的特点，这种释药规律符合抗癌药物的用药原则，可用于构建可注射丝素原位凝胶缓释体系。季铵盐类抗菌剂作为凝胶促进剂，能够诱导丝素蛋白水溶液快速原位凝胶化。利用X射线衍射、红外光谱、扫描电镜、差热分析和圆二色光谱等手段对所制丝素水凝胶的结构、热稳定、降解性、抗菌性能及其形成机理进行了探究。研究结果表明，季铵盐促发形成的丝素水凝胶为β-折叠片层结构，凝胶内部形貌为多孔的三维网状结构，且对革兰氏阳性菌和阴性菌都有很明显的抗菌效果。同时由体外降解、差热分析结果可知，季铵盐引发丝素蛋白溶液快速形成水凝胶，其三维交联结构在水中可以降解，在蛋白酶液中更容易降解。季铵盐在水凝胶中主要以无定形或亚稳态晶体状态存在，容易扩散释放，达到较好的抗菌效果，这种抗菌性的原位丝素蛋白水凝胶有望可以用于外科伤口敷料。
[Abstract]:Injectable in situ fibroin (SF) hydrogel has the advantages of minimal surgical trauma and potential application in various biomaterials. As an ideal injectable in situ hydrogel material, it needs to be quickly gelatinized to meet the need of the gel forming immediately after injection in vivo. The gelation of silkworm fibroin by two kinds of small molecular surfactants, such as sodium dodecyl sulfate, sodium (SDS), sodium dodecyl ether sulfate, sodium (AES), and quaternary ammonium cationic surfactants, has been studied in this paper. The influence of the structure and properties of silk fibroin gel was discussed, and the mechanism of silk fibroin in situ gelation was discussed. Sulfate anionic surfactants can shorten the gelation time of silk fibroin, and its promotion degree is directly related to the length of its hydrophobic hydrocarbon chain, when the hydrophobic chain is short (? 8), The gelation rate of silk fibroin increased with the extension of hydrocarbon chain. The mechanism of rapid gelation of silk fibroin initiated by SDS was studied in detail. The structure, mechanical properties, degradation and in vitro release of sulfate anionic surfactant / silk fibroin composite hydrogel were characterized. The results of drug release showed that the release of adriamycin in vitro by SDS/SF,AES/SF gel stimulated by SDS,AES was relatively large in the early stage (1-10 days) and lasted for a long time. But in the late stage (10-38 days), the release was slow and the rate was constant. This release law was consistent with the principle of anti-cancer drugs, and could be used to construct the injectable silk fibroin in-situ gel sustained release system. Quaternary ammonium salts as gel promoters can induce rapid in situ gelation of silk fibroin solution. The structure, thermal stability, biodegradability, antibacterial properties and formation mechanism of silk fibroin hydrogel were investigated by means of X-ray diffraction, infrared spectroscopy, scanning electron microscope, differential thermal analysis and circular dichroism spectroscopy. The results showed that the silk fibroin hydrogel induced by quaternary ammonium salt was a 尾 -folded lamellar structure, and the internal morphology of the gel was a porous three-dimensional reticular structure, and it had obvious antibacterial effect against both Gram-positive and negative bacteria. At the same time, the results of in vitro degradation and differential thermal analysis showed that quaternary ammonium salt initiated the rapid formation of hydrogel in silk fibroin solution, its three-dimensional cross-linking structure could be degraded in water, and it was easier to degrade in protease solution. Quaternary ammonium salts exist mainly in amorphous or metastable crystal state in hydrogels, which are easy to diffuse and release to achieve better antibacterial effect. This antibacterial in situ fibroin hydrogel is expected to be used in surgical wound dressing.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08

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