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  臨床上的血樣采集往往需要多次抽血，例如，口服糖耐量測試需要在3小時內取血5次，常用的方法是利用注射器對患者進行反復穿刺取血，不僅給患者帶來了很大的痛苦和心理影響，也會增加感染的風險。留置針作為臨床上常用的短期植入裝置可以避免反復穿刺，減少患者痛苦，但由于蛋白的非特異性吸附等原因出現的凝血問題以及拔針后的出血仍然是一個難以解決的問題。雖然臨床常用的肝素封管手段可以避免凝血問題，但是隨之帶來的凝血功能障礙和潛在的出血風險尚無法避免。此外，血糖檢測等血液測試均不能使用肝素。傳統上，抗凝血和止血是一個不可調和的矛盾，所以目前的植入材料均只具備單一的抗凝血或止血功能，而如何在同一材料上同時實現抗凝血和止血始終無法解決。

  基于上述考慮，天津大學劉文廣教授團隊開發了一種具有可調節抗凝血-止血功能的智能留置針，該團隊首先在留置針內表面修飾了一層多巴胺底漆，并通過磁場和非共價鍵相互作用將一種具有核殼結構的多巴胺-肝素包裹的磁性納米粒子（FeNPs-HepDA）有序地固定于多巴胺底漆之上，然后在留置針外層涂覆鄰苯二酚修飾的殼聚糖（CHCS）形成薄膜。在外加磁場作用下，由于納米粒子的有序排列和固定化，可以顯著提高局部抗凝血效果且納米粒子不會進入血液循環，在保持血流通暢的情況下3小時內可以取血6次。當需要拔針的時候，只需提前撤走磁場10分鐘，納米粒子會發生局部團聚并少量釋放到血液中，降低局部抗凝血性能，外層殼聚糖可以有效富集血小板并在拔針時于穿刺部位形成一層止血薄膜防止血液流失。值得一提的是，這種可調控的抗凝血和止血功能可以通過體外磁場的變化來控制，并且通過對兔主要臟器的病理觀察和肝功腎功能檢測證實其具有良好的體內安全性。

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.

  這種應用于智能留置針的抗凝血-止血隨需切換策略為開發新型兼具抗凝血和止血功能的生物材料和醫療器械提出了新的設計思路。

  目前上述工作已發表在《Materials Horizons》上，論文第一作者為天津大學材料學院博士生吳元昊，通訊作者為天津大學材料學院劉文廣教授。

  論文連接：https://pubs.rsc.org/en/Content/ArticleLanding/2019/MH/C9MH01619H#!divAbstract