Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, 4072, Australia.
University of Queensland Centre for Clinical Research, The University of Queensland, Herston, QLD, 4029, Australia.
Adv Healthc Mater. 2022 Aug;11(15):e2200574. doi: 10.1002/adhm.202200574. Epub 2022 Jun 9.
Uncontrolled bleeding from traumatic injury remains the leading cause of preventable death with loss of balance between blood clotting (coagulation) and blood clot breakdown (fibrinolysis). A major limitation of existing hemostatic agents is that they require a functioning clotting system to control the bleeding and are largely based on gauze delivery scaffolds. Herein, a novel rapid wound sealant, composed of two recombinant snake venom proteins, the procoagulant ecarin, to rapidly initiate blood clotting and the antifibrinolytic textilinin, to prevent blood clot breakdown within a synthetic thermoresponsive hydrogel scaffold is developed. In vitro, it is demonstrated that clotting is rapidly initiated with only nanomolar concentrations of venom protein and clot breakdown is effectively inhibited by textilinin. A stable clot is formed within 60 s compared to normal clot formation in 8 min. In vivo studies reveal that the snake venom hydrogel rapidly controls warfarin-induced bleeding, reducing the bleed volume from 48% to 12% and has demonstrated immune compatibility. A new class of hemostatic agents that achieve formation of rapid and stable blood clots even in the presence of blood thinners is demonstrated here.
创伤性损伤导致的无法控制的出血仍然是可预防死亡的主要原因，其原因在于血液凝结（凝血）和血液凝块分解（纤维蛋白溶解）之间失去了平衡。现有的止血剂的主要局限性在于它们需要一个正常运作的凝血系统来控制出血，并且主要基于纱布输送支架。在此，开发了一种新型快速伤口密封剂，由两种重组蛇毒蛋白组成，促凝血酶原 ecarin 可快速启动血液凝结，抗纤维蛋白溶酶 textilinin 可防止合成热响应水凝胶支架内的血液凝块分解。体外实验表明，仅需纳摩尔浓度的蛇毒蛋白即可快速启动凝血，并且 textilinin 可有效抑制凝血分解。与正常 8 分钟的凝血形成相比，在 60 秒内形成稳定的凝块。体内研究表明，蛇毒水凝胶可迅速控制华法林诱导的出血，使出血量从 48%减少到 12%，并表现出免疫相容性。这里展示了一类新型止血剂，即使在存在血液稀释剂的情况下，也能迅速形成快速且稳定的血栓。
