Mecwan Marvin, Haghniaz Reihaneh, Najafabadi Alireza Hassani, Mandal Kalpana, Jucaud Vadim, John Johnson V, Khademhosseini Ali
Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA.
Biomater Sci. 2023 Jan 31;11(3):949-963. doi: 10.1039/d2bm01559e.
Hemorrhage is the leading cause of death following battlefield injuries. Although several hemostats are commercially available, they do not meet all the necessary requirements to stop bleeding in combat injuries. Here, we engineer thermoresponsive shear-thinning hydrogels (T-STH) composed of a thermoresponsive polymer, poly(-isopropyl acrylamide) (p(NIPAM)), and hemostatic silicate nanodisks, LAPONITE®, as minimally invasive injectable hemostatic agents. Our T-STH is a physiologically stable hydrogel that can be easily injected through a syringe and needle and exhibits rapid mechanical recovery. Additionally, it demonstrates temperature-dependent blood coagulation owing to the phase transition of p(NIPAM). It decreases blood clotting times over 50% at physiological temperatures compared to room temperature. Furthermore, it significantly prevents blood loss in an bleeding model at different blood flow rates (1 mL min and 5 mL min) by forming a wound plug. More importantly, our T-STH is comparable to a commercially available hemostat, Floseal, in terms of blood loss and blood clotting time in an rat liver bleeding model. Furthermore, once the hemorrhage is stabilized, our T-STH can be easily removed using a cold saline wash without any rebleeding or leaving any residues. Taken together, our T-STH can be used as a first aid hemostat to treat external hemorrhages in emergency situations.
出血是战场受伤后导致死亡的主要原因。尽管有几种止血剂已在市场上销售,但它们并不满足在战伤中止血的所有必要要求。在此,我们设计了一种热响应性剪切变稀水凝胶(T-STH),它由热响应性聚合物聚(N-异丙基丙烯酰胺)(p(NIPAM))和止血性硅酸盐纳米盘LAPONITE®组成,作为微创可注射止血剂。我们的T-STH是一种生理稳定的水凝胶,可通过注射器和针头轻松注射,并具有快速的机械恢复能力。此外,由于p(NIPAM)的相变作用,它还表现出温度依赖性的血液凝固。与室温相比,在生理温度下它可使血液凝固时间缩短50%以上。此外,通过形成伤口堵塞物,它能在不同血流速度(1 mL/min和5 mL/min)的出血模型中显著防止失血。更重要的是,在大鼠肝脏出血模型中,就失血量和血液凝固时间而言,我们的T-STH与市售止血剂弗洛塞尔相当。此外,一旦出血稳定,我们的T-STH可用冷盐水冲洗轻松去除,不会再次出血或留下任何残留物。综上所述,我们的T-STH可作为急救止血剂用于紧急情况下治疗外部出血。