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静脉内合成血小板(SynthoPlate)纳米结构减少出血,并改善创伤性动脉出血猪模型中的“黄金小时”存活率。

Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

机构信息

Department of Pathology, Case Western Reserve University, Cleveland, OH, 44106, USA.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.

出版信息

Sci Rep. 2018 Feb 15;8(1):3118. doi: 10.1038/s41598-018-21384-z.

Abstract

Traumatic non-compressible hemorrhage is a leading cause of civilian and military mortality and its treatment requires massive transfusion of blood components, especially platelets. However, in austere civilian and battlefield locations, access to platelets is highly challenging due to limited supply and portability, high risk of bacterial contamination and short shelf-life. To resolve this, we have developed an I.V.-administrable 'synthetic platelet' nanoconstruct (SynthoPlate), that can mimic and amplify body's natural hemostatic mechanisms specifically at the bleeding site while maintaining systemic safety. Previously we have reported the detailed biochemical and hemostatic characterization of SynthoPlate in a non-trauma tail-bleeding model in mice. Building on this, here we sought to evaluate the hemostatic ability of SynthoPlate in emergency administration within the 'golden hour' following traumatic hemorrhagic injury in the femoral artery, in a pig model. We first characterized the storage stability and post-sterilization biofunctionality of SynthoPlate in vitro. The nanoconstructs were then I.V.-administered to pigs and their systemic safety and biodistribution were characterized. Subsequently we demonstrated that, following femoral artery injury, bolus administration of SynthoPlate could reduce blood loss, stabilize blood pressure and significantly improve survival. Our results indicate substantial promise of SynthoPlate as a viable platelet surrogate for emergency management of traumatic bleeding.

摘要

创伤性非压迫性出血是导致平民和军人死亡的主要原因,其治疗需要大量输注血液成分,特别是血小板。然而,在艰苦的平民和战场环境中,由于供应有限和便携性差、细菌污染风险高以及保质期短,血小板的获取极具挑战性。为了解决这个问题,我们开发了一种可静脉给药的“合成血小板”纳米构建体(SynthoPlate),它可以模拟和放大身体的自然止血机制,特别是在出血部位,同时保持全身安全性。此前,我们已经在小鼠非创伤性尾部出血模型中报道了 SynthoPlate 的详细生化和止血特性。在此基础上,我们旨在评估 SynthoPlate 在创伤性出血后“黄金一小时”内紧急给药时在股动脉猪模型中的止血能力。我们首先在体外对 SynthoPlate 的储存稳定性和灭菌后生物功能进行了表征。然后将纳米构建体静脉给药给猪,并对其全身安全性和生物分布进行了表征。随后,我们证明了在股动脉损伤后,SynthoPlate 的单次推注给药可以减少失血量、稳定血压并显著提高存活率。我们的结果表明,SynthoPlate 作为一种可行的血小板替代品,有望用于创伤性出血的紧急治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f24f/5814434/a44dac9633dc/41598_2018_21384_Fig1_HTML.jpg

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