【作者】 陈蕾；

【导师】 闫玉华；

【作者基本信息】 武汉理工大学 ， 材料学， 2006， 硕士

【摘要】 论文研究了采用溶剂挥发法制备的用于修复周围神经损伤的聚乳酸复合膜。选用外消旋聚乳酸(PDLLA)作为基体材料,分别通过物理共混(添加一定比例的壳聚糖和钙磷无机盐粉末及神经生长因子NGF)和表面截留改性的方法制备出具有良好降解性能和细胞亲和性的复合膜。 通过对复合膜制备工艺、成膜性能影响因素的研究,纯聚乳酸分别与不同含量壳聚糖(CHS)、β-磷酸三钙(β-TCP)组成复合膜进行体外降解实验,测定降解介质的pH值变化、复合膜质量变化,考虑降解速率与神经再生速度的匹配,优化复合材料的组成成分和比例,得出:在20℃、40%湿度下,聚乳酸分子量范围为:10×104～40×10~4,以乙酸乙酯为溶剂配制10%的聚乳酸溶液,采用溶剂挥发法、超声波分散粒径<63μm,含量为30%的CHS(5～8万)粉末和5%的β-TCP粉末,可以制备出性能良好的复合膜。 对复合膜进行体内外降解实验,测定降解过程中降解介质pH值的变化、复合膜的质量损耗率、聚乳酸分子量的变化,对降解产物进行XRD表征,观察复合膜的大体形貌及微观结构的变化。结果表明:聚乳酸降解过程中无结晶型低聚物产生,测定聚乳酸重均分子量中出现的双峰结构及体内降解3个月后PDLLA膜呈现的中空透明状都说明本实验中聚乳酸的降解是不均匀水解。由于膜材很薄,酸自催化效应较小,因此其降解产生的酸性不明显。一定比例β-TCP和CHS粉末的加入,可以适当增强膜材的强度,中和聚乳酸降解产物的酸性,有效调节降解介质的pH值使其维持在中性。β-TCP、CHS粉末在体外弱酸性环境下,才被促进溶解或发生酸水解。而在动物体内由于酶解和细胞的参与,β-TCP、CHS粉末可以更快的降解、代谢。因此,复合材料的动物体内降解要比体外模拟体液中的降解要快。另外,神经生长因子NGF的加入对材料降解过程中pH值的变化及复合膜的质量损耗率均有一定影响。复合膜的亲/疏水性评价表明:添加了神经生长因子NGF和CHS、β-TCP粉末的复合膜的亲水性均有大的改善。 PDLLA/NGF复合膜修复缺损神经的动物实验采用大鼠坐骨神经缺损模型,分别用自体神经移植和自体神经移植并局部放置PDLLA/NGF复合膜修复缺损神经,于术后6个月观察神经再生情况。结果显示:在神经缺损的局部放置含更多还原

【Abstract】 A kind of poly (d, 1-lactic acid) composite membrane which was prepared by solvent volatilization method was investigated to repair peripheral nerve defect. Poly (d, 1-lactic acid) was selected as the matrix, physical mix (incorporating with chitosan, β-tricalcium phosphate (β-TCP) powder and nerve growth factor (NGF)) and surface entrapment methods were adopted respectively to prepare composite membranes which have good degradation characteristics and cytocompatibility.To study the most suitable composite membrane for repairing nerve defect, the preparation process of the composite membrane and factors in influence membrane performance were studied;the pH value of degradation medium, weight loss of pure PDLLA and its composite membrane with CHS and P-TCP were observed during the degradation in vitro. In view of the degradation speed of the composite membrane matching the nerve restoring speed, we optimized the component and proportion of composite membrane and had the results: we can prepare composite membrane with good performance by solvent volatilization method and the ultrasonic dispersal technique under 20℃ and 40% humidity.The range of molecular weight of PDLLA was selected as 10×10~4~40×10~4, using ethyl acetate as solvent to confect PDLLA solution with 10% concentration, adding CHS and P-TCP powder which the grain size less than 63μm,content ratio was fixed respectively at 30% and 5%.The pH value of degradation medium, weight loss ratio of composite membrane, the variation of molecular weight of PDLLA were determinated during the degradation in vitro .We also did the XRD for degradation products and observed the variation of the morphology and microstructure of composite membrane.The results showed that: no crystallized oligomers formed during the degradation of PDLLA. A bimodal distribution which was obtained during the determination of weight average molecular weight of PDLLA and hollow membrane structure which was appeared at the degradation of PDLLA in 3 months in vivo both showed that the mechanism of hydrolytic degradation of PDLLA is heterogeneous degradation.Because the membranes are thin, the acid autocatalytic effect is not very visible. The acidity whichproduced by degradation is also not visible. Adding appropriate content of CHS and P-TCP powder can reinforce the strength of membrane, neutralize the acidity which produced by degradation products, availably adjust the pH value of the degradation medium to keep at neuter. The P-TCP and CHS powder can be promoted to dissolve or occur acid hydrolyze only at the weak acid environment in vitro.But when in animal vivo, because of the existence of enzymatic degradation and function of cells, the CHS and P-TCP powder can degradate and metabolize more quickly.So the degradation in animal vivo was obvious quicker than the degradation at the simulation body fluid in vitro.In addition, incorporating with NGF had definite influence on the variation of pH value and the weight loss ratio of composite membrane during the degradation. Hydrophilicity/hydrophobicity determinations of composite membrane showed that: adding NGF and CHS^ P-TCP powder both can improve the hydrophilicity of composite membrane.The animal experiment was to repair nerve defect by using PDLLA/NGF composite membrane. We adopted rat sciatic nerve transaction model to kept a 1 Omm nerve defect, then these defects were repaired by using nerve autografting > nerve autografting and at part placed PDLLA/NGF composite membrane.Function repair of sciatic nerve regeneration was evaluated at 6 months.The results showed that at the nerve defect part placing the composite membrane which contained NGF also can accelerate the nerve regeneration.The analysis of IR, XPS, atomic force microscopy (AFM), contact angle measurement and degradation experiment in vitro all showed that it could obtain stable hydrophilic surface on PDLLA matrix separately via chitosan and sodium alginate entrapment.The cytocompatibility was improved, and the degradation performance can be appropriately adjusted.更多还原