立构复合协同表面交联对聚乳酸微孔膜的结晶与微孔结构演变及表面相容性调控机理研究

The bio-based polylactide (PLA), with the good biocompatibility, degradable small molecules nontoxicity, a certain using life, excellent mechanical properties and low price, is a promising new membrane material in the application of disposable hemodialysis medical membranes. This project is aiming to solve the problems of weak thermal stability, hydrophilicity and hemocompatibility for PLA microporous membrane. From viewpoints of the molecular structure designing, chain segments and aggregation controlling as well as the membrane surface chemistry and its micro/nano structure regulation, we expect to enhance the crystallization properties, hydrophilicity, and blood anticoagulation in virtue of the combination stereocomplex and surface crosslinking. Correspondingly, the thermal deformation temperature, separation and hemocompatibility of PLA membrane are resulting improved. We will firstly discuss the crystallization evolution of PLA membrane on its heat resistance, mechanical properties and microporous structure as well as their competitive relation; Secondly, we will focus on the effect of surface crosslinking on the hydrophilicity, charge, surface micro/nano structure, hemocompatibility and stability of PLA membrane as well as the surface inducing crystallization on the PLA membrane microporous structure and separation properties; Lastly, the key scientific issue involving the interaction law between crystallization evolution and microporous structure and the relative between compatibility and membrane dialysis properties are resolved via the key technology of the combination stereocomplex and surface crosslinking. This project will provide a reasonable method to controllably fabricate and develop the heat resistant PLA hemodialysis membrane, and as a result break through the limitation of PLA in the application of hemodialysis membrane.

聚乳酸由于其生物来源及可控降解等特点，在一次性生物医用及水净化领域具有潜在应用及研究价值。本课题拟针对聚乳酸微孔膜的耐热性稳定性及亲水相容性差的关键问题，通过立构复合协同表面交联技术，提高聚乳酸微孔膜的结晶度，进而调控聚乳酸微孔膜的耐热稳定性及亲水和血液相容性。具体通过逐步聚合合成软、硬段可调的聚氨酯(PU)与D型聚乳酸嵌段共聚物(PDLA-PU)，并进一步利用溶液相转化过程中的立构复合效应调控L型聚乳酸(PLLA)的结晶并提高其耐热、韧性和微孔梯度分布。通过基于硅化学的表面交联作用在聚乳酸微孔膜表面固定亲水及两性离子类肝素层，以提高膜的血液相容性。重点研究聚氨酯嵌段共聚物在相转化过程中的立构复合作用对膜结晶和微孔结构竞争演变机制，以及表面交联对聚乳酸微孔膜的相容性调控规律。最终通过立构复合协同表面交联技术建立聚乳酸微孔膜结晶演变-微孔结构-与膜相容性的系统作用规律。

聚乳酸由于其生物来源及可控降解等特点，在一次性生物医用及水净化领域具有潜在应用及研究价值。本课题拟针对聚乳酸微孔膜的耐热性稳定性、 亲水性和血液相容性差的关键问题，通过基于硅化学的表面交联作用在聚乳酸微孔膜表面固定亲水及肝素层，以提高膜的亲水性和血液相容性。PLA 膜的耐热性、亲水性和血液相容性通过表面交联诱导结晶的方法制备，这个过程包括两个主要的反应： N-乙烯基-2-吡咯烷酮（NVP）与乙烯基三乙氧基硅烷（VTES）的共聚反应、之后的在 PLA 膜表面水解缩合。可以发现共聚物P(VP-VTES)水热交联且诱导 PLA 膜结晶。表面结晶明显的改善了膜的耐热性，能保持膜的形貌。结晶度 χc 为~37%的改性 PLA 膜在 100℃下热处理 5min 还可以保持几乎不变尺寸和形态。血液相容性的提高通过凝固时间和血液复钙时间的延长来验证，这与亲水性的增加是一致的。所有的结果表明表面交联诱导结晶的方法同时改善了耐热性和血液相容性，意味着这对制备稳健和相容性的 PLA 膜是一种很有前景的方法。透析膜的血液相容性被认为是影响透析法治疗肾脏问题的关键因素。考虑到这一方面，常用的抗凝剂肝素在临床上可以通过缩水甘油醚反应直接结合聚乳酸（PLA）膜来提高血液相容性。一种新型的预聚物 P(VP-VTES-GMA)通过自由基聚合反应首次合成。包含 GMA 链段的预聚物表面交联能使膜通过缩水甘油醚反应固定肝素。由 APTT、 PRT、 PT、 FIB 和血小板吸附全面研究血液相容性。 尿素、肌酸酐、溶菌酶和牛血清白蛋白的清除率由模拟透析性能测定。所有的结 果表明肝素的共价结合是 PLA 膜有极好的血液相容性、亲水性、耐热性和透析.性能。