临床上的血样采集往往需要多次抽血，例如，口服糖耐量测试需要在3小时内取血5次，常用的方法是利用注射器对患者进行反复穿刺取血，不仅给患者带来了很大的痛苦和心理影响，也会增加感染的风险。留置针作为临床上常用的短期植入装置可以避免反复穿刺，减少患者痛苦，但由于蛋白的非特异性吸附等原因出现的凝血问题以及拔针后的出血仍然是一个难以解决的问题。虽然临床常用的肝素封管手段可以避免凝血问题，但是随之带来的凝血功能障碍和潜在的出血风险尚无法避免。此外，血糖检测等血液测试均不能使用肝素。传统上，抗凝血和止血是一个不可调和的矛盾，所以目前的植入材料均只具备单一的抗凝血或止血功能，而如何在同一材料上同时实现抗凝血和止血始终无法解决。

  基于上述考虑，天津大学刘文广教授团队开发了一种具有可调节抗凝血-止血功能的智能留置针，该团队首先在留置针内表面修饰了一层多巴胺底漆，并通过磁场和非共价键相互作用将一种具有核壳结构的多巴胺-肝素包裹的磁性纳米粒子（FeNPs-HepDA）有序地固定于多巴胺底漆之上，然后在留置针外层涂覆邻苯二酚修饰的壳聚糖（CHCS）形成薄膜。在外加磁场作用下，由于纳米粒子的有序排列和固定化，可以显著提高局部抗凝血效果且纳米粒子不会进入血液循环，在保持血流通畅的情况下3小时内可以取血6次。当需要拔针的时候，只需提前撤走磁场10分钟，纳米粒子会发生局部团聚并少量释放到血液中，降低局部抗凝血性能，外层壳聚糖可以有效富集血小板并在拔针时于穿刺部位形成一层止血薄膜防止血液流失。值得一提的是，这种可调控的抗凝血和止血功能可以通过体外磁场的变化来控制，并且通过对兔主要脏器的病理观察和肝功肾功能检测证实其具有良好的体内安全性。

Fig. 1 Design of a smart indwelling needle with on-demand switchable anticoagulant and hemostatic property. First, the inner surface of indwelling needle was coated with polydopamine primer formed from self-polymerization of dopamine, followed by modification with FeNPs-HepDA. Then catechol-functionalized chitosan (CHCS) was coated on the outside surface of cannula. This doubly modified needle was injected into the ear vein of rabbit. Blood could be drawn out in 3 h under a magnetic field. When the magnetic was removed, the FeNPs-HepDA was aggregated and released to circulating blood; after 10 min, the needle was pulled out. Under this condition, the external CHCS could prevent bleeding.

Fig. 2 Anticoagulant capability and hemostatic activity of the modified indwelling needle for in vivo model. a) Images showing the anticoagulant process and blood loss in rabbit ear vein. Blood was drawn out every 30 min to measure the anticoagulant potency. The indwelling needle sealed with heparin, which is the most widely used method to maintain the antithrombotic effect of biomedical devices in clinical, was set as the positive control. Once the blood could not be drawn out (meaning the occurrence of blood coagulation), the needle was pulled out from the vein, followed by measuring the blood loss. b-e) Histology section images of a rabbit ear vein after extraction of the indwelling needle. Vertical and horizontal section of blood vessel was displayed. The red arrows represented the residual CHCS film.

  这种应用于智能留置针的抗凝血-止血随需切换策略为开发新型兼具抗凝血和止血功能的生物材料和医疗器械提出了新的设计思路。

  目前上述工作已发表在《Materials Horizons》上，论文第一作者为天津大学材料学院博士生吴元昊，通讯作者为天津大学材料学院刘文广教授。

  论文连接：https://pubs.rsc.org/en/Content/ArticleLanding/2019/MH/C9MH01619H#!divAbstract