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类似栗子的大棘刺触发止血:一种基于刺穿红细胞的特征性机制。

Chestnut-like macro-acanthosphere triggered hemostasis: a featured mechanism based on puncturing red blood cells.

机构信息

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.

出版信息

Nanoscale. 2021 Jun 3;13(21):9843-9852. doi: 10.1039/d1nr01148k.

Abstract

Acute hemorrhage that occurs after trauma is a life-threatening condition. Hence, to halt massive bleeding, there is a critical need to develop a suitable therapy. In this study, we developed self-propelling chestnut-like particles (Pro-MAS) comprising a macro-acanthosphere (MAS) coated with calcium carbonate and protonated tranexamic acid to puncture red blood cells (RBCs) and thus activate hemostasis. In vitro assessments revealed that Pro-MAS was biocompatible, biodegradable, and nontoxic; furthermore, it was capable of puncturing RBCs to release procoagulants and activate platelet aggregation for hemostasis. Animal tests showed that self-propelling Pro-MAS effectively traveled through blood flow to the deep ends of wounds; hemorrhage was controlled within 90 s and 4 min in the injured liver and bleeding femoral artery, respectively. Compared with a commercial hemostat, superior hemostasis was achieved with Pro-MAS, which could be ascribed to its functional and structural features. Overall, traveling Pro-MAS possessed sufficient impact force to puncture RBCs and sufficient momentum to reach the targeted bleeding sites. The present study demonstrated the ability of a novel platform, self-propelling MAS particles, to trigger hemostasis by puncturing RBCs. To the best of our knowledge, this is the first trial in which the release of endogenous procoagulants is promoted without the addition of exogenous procoagulants for severe hemorrhage control.

摘要

创伤后发生的急性出血是一种危及生命的情况。因此,迫切需要开发一种合适的治疗方法来止血。在这项研究中,我们开发了自推进的板栗状粒子(Pro-MAS),它由涂有碳酸钙和质子化氨甲环酸的大刺球(MAS)组成,能够刺穿红细胞(RBC)并激活止血。体外评估显示,Pro-MAS 具有生物相容性、可生物降解性和低毒性;此外,它能够刺穿 RBC 释放促凝剂并激活血小板聚集以止血。动物试验表明,自推进的 Pro-MAS 能够有效地穿透血流到达伤口深处;在受伤的肝脏和出血的股动脉中,分别在 90 秒和 4 分钟内控制了出血。与商业止血剂相比,Pro-MAS 实现了更好的止血效果,这可以归因于其功能和结构特征。总的来说,行进的 Pro-MAS 具有足够的冲击力来刺穿 RBC,并具有足够的动力到达目标出血部位。本研究证明了一种新型平台,自推进的 MAS 颗粒,通过刺穿 RBC 触发止血的能力。据我们所知,这是第一个在不添加外源性促凝剂的情况下促进内源性促凝剂释放以控制严重出血的试验。

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