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快速共价凝胶化与坚固的湿粘性粉末相结合:一种用于动态和高压创伤环境中急性大量出血控制的新方法。

Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High-Pressure Wound Environments.

机构信息

Key Laboratory for Ultrafine Materials of Ministry of Education, School of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.

出版信息

Small. 2024 Aug;20(33):e2311859. doi: 10.1002/smll.202311859. Epub 2024 Apr 21.

DOI:10.1002/smll.202311859
PMID:38643382
Abstract

The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound environments. Traditional self-gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self-gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises ε-polylysine (ε-PLL) and 4-arm polyethylene glycol succinyl succinate (4-arm-PEG-NHS) forming the hydrogel framework. NaHPO functions as the "H sucker" to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross-linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage.

摘要

在急诊医学中,寻找高效的止血剂至关重要,特别是在处理动态高压伤口环境中的大量出血时。传统的自凝胶粉末由于易于应用和快速作用而具有优势,但在这种具有挑战性的条件下仍存在不足。为了弥补这一差距,研究引入了一种新型的自凝胶粉末,它结合了超快的共价凝胶化和强大的湿粘附性,在急性出血控制方面取得了重大进展。该三元体系由ε-聚赖氨酸(ε-PLL)和 4 臂聚乙二醇琥珀酰琥珀酸酯(4-臂-PEG-NHS)组成水凝胶骨架。NaHPO 作为“H 吸盘”加速酰胺化反应,使凝胶时间缩短至 10 秒以内,这对于立即限制失血至关重要。此外,PEG 链的亲水性有助于界面血液的有效吸收,增加生成水凝胶的交联密度并增强其组织结合,从而产生优异的机械和湿粘附性能。体外实验揭示了优化配方的出色组织顺应性、促凝血活性、生物相容性和抗菌功效。在猪心脏损伤和动脉穿刺模型中,它优于商业止血剂 Celox,证实了其快速有效的止血效果。总之,本研究提出了一种变革性的止血方法,为大量出血的紧急管理提供了可靠有效的解决方案。

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