基于抗结壳性能的硫酸软骨素膜制备及其机制研究

The encrustation and induced infection severely impact on the clinic therapeutic effectiveness and service life of urinary stents with long-term indwelling. The explanations to elucidate the mechanism of encrustation or infection-inhibiting materials are not available due to the particularity and complexity of urine. The fast formation of conditioning film on urinary stents after implantation is one of the critical fact for encrustation. In this project, the prevention of the formation of the conditioning film is raised to basically study and resolve the problems of encrustation and infection-inhibition and illustrate correlative mechanism. Thus, the diamine is introduced as a spacer. Chondroitin sulfate(CS), a polyanion, is used as the functional molecule. A series of negatively charged films with special structure and property are designed and prepared on polyurethane(PU) film. Subsequently,based on these functional films, the effects of charge density, hydrophility, roughness and pliability on the diffusion of charged ions and macromolecules are investigated to reveal the mechanism of preventing the formation of conditioning film. The adhesion and growth of bacteria, the formation, growth and aggregation of calcium oxalate crystals are further investigated to indicate the mechanism of anti-encrustation. Subsequentely, the theoretical frame of modified film, condition film and encrustation is devloped. The results will directly provide theoretical and practical basis to develop novel urinary stents with significant anti-encrustation.

硬性结壳并诱发感染是影响输尿管支架的临床治疗效果和寿命的根本原因。由于尿液环境的特殊性和复杂性，对于结壳和支架材料抑制感染等机理仍不清晰。支架植入体内后快速形成的条件膜是引起结壳的关键因素之一，本项目从防止条件膜形成的角度，研究和解决结壳和抑制感染问题，并阐释相关机理。通过设计和制备具有特殊结构和性能的负电膜：以聚氨酯为基材，聚阴离子硫酸软骨素（CS）作为功能分子，以二胺类化合物作为间隔基连接CS大分子，制备系列表面负电荷密度、亲水性、粗糙度，柔性不同的CS膜，以此来研究膜表面性能变化对尿液中带电离子和大分子物质扩散的影响规律，揭示条件膜形成机制和CS膜对抗条件膜形成的规律和机制，进而研究该膜对细菌粘附和生长及对草酸钙晶体形成、生长和聚集的影响，探索和揭示抗结壳机制，并建立膜表面结构和性能－条件膜－结壳的理论框架，为设计新型的具有抗结壳功能的输尿管支架提供理论和制备依据。

输尿管支架上的结壳和由此诱发的感染严重影响了其治疗效果和使用寿命。当支架植入体内后条件膜的快速形成是引起结壳的关键因素之一。在本研究重，我们制备了硫酸软骨素改性的聚氨酯(PU-CS)抗污表面。通过改变硫酸软骨素接枝密度从而改变表面的各种性能，如亲水性，粗糙度等，用来研究不同表面的条件膜组成，以及条件膜性能对细菌粘附和无机盐沉积的影响。研究结果表明，随着硫酸软骨素接枝密度的增加，条件膜的组成趋近与更少的蛋白和多糖。覆盖相应条件膜的PU-CS粗糙度，水接触角和zeta电位也随之降低。接枝密度为3.7 g/cm2的PU-CS(3)具有最好的抑菌效果和最少的无机盐沉积。而且在实际尿液中考察21天，PU-CS(3)上无机盐沉积最少且最小，细菌基本检测不到。通过比较细菌粘附在PU-CS原膜或膜上覆盖蛋白或条件膜的变化，发现蛋白有利于细菌粘附，而多糖具有抑制作用。而且粗糙度小和亲水性好的表面也有利于防止细菌粘附和无机盐沉积。