Nanobioscience, Agharkar Research Institute, Pune 411004 India; Department of Biotechnology, Savitribai Phule Pune University, Pune 411007 India.
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Pune 411008 India.
Colloids Surf B Biointerfaces. 2021 Feb;198:111454. doi: 10.1016/j.colsurfb.2020.111454. Epub 2020 Nov 6.
Uncontrolled hemorrhage often causes death during traumatic injuries and halting exsanguination topically is a challenge. Here, an efficient multimodal topical hemostat was developed by (i) ionically crosslinking chitosan and gelatin with sodium tripolyphosphate for (ii) fabricating a robust, highly porous xerogel by lyophilization having 86.7 % porosity, by micro-CT and large pores ∼30 μm by SEM (iii) incorporating 0.5 mg synthesized silica nanoparticles (SiNPs, 120 nm size, -22 mV charge) and 2.5 mM calcium in xerogel composite that was confirmed by FTIR analysis with peaks at 3372, 986 and 788 cm, respectively. XPS analysis displayed the presence of SiNPs (Si2p peak for silicon) and calcium (Ca2p1, Ca2p3 transition peaks) in the composite. Interestingly, in silico percolation simulation for composite revealed interlinked 800 μm long-conduits predicting excellent absorption capacity and validated experimentally (640 % of composite dry weight). The composite achieved >16-fold improved blood clotting in vitro than commercial Celox and Gauze through multimodal interaction of its components with RBCs and platelets. The composite displayed good platelet activation and thrombin generation activities. It displayed high compressive strength (2.45 MPa) and withstood pressure during application. Moreover, xerogel composite showed high biocompatibility. In vivo application of xerogel composite to lethal femoral artery injury in rats achieved hemostasis (2.5 min) significantly faster than commercial Celox (3.3 min) and Gauze (4.6 min) and was easily removed from the wound. The gamma irradiated composite was stable till 1.5 yr. Therefore, the xerogel composite has potential for application as a rapid topical hemostatic agent.
在创伤中,无法控制的出血常常导致死亡,而局部止血是一个挑战。在这里,通过(i)用三聚磷酸钠离子交联壳聚糖和明胶,(ii)通过冷冻干燥制造出具有 86.7%孔隙率、通过微 CT 和 SEM 观察到的大孔约 30 μm 的坚固、高多孔性水凝胶,(iii)在水凝胶复合材料中加入 0.5 mg 合成的二氧化硅纳米颗粒(SiNPs,粒径为 120nm,带负 22mV 电荷)和 2.5mM 钙,通过傅里叶变换红外光谱分析(FTIR)得到证实,分别在 3372、986 和 788cm 处有峰。X 射线光电子能谱分析(XPS)显示复合材料中存在 SiNPs(硅的 Si2p 峰)和钙(Ca2p1、Ca2p3 跃迁峰)。有趣的是,复合材料的计算机渗流模拟显示,互联的 800μm 长导管预测了优异的吸收能力,并通过实验验证(复合材料干重的 640%)。与商业 Celox 和纱布相比,该复合材料通过其与 RBC 和血小板的多模态相互作用,在体外实现了 >16 倍的血液凝结改善。该复合材料显示出良好的血小板激活和凝血酶生成活性。它显示出高抗压强度(2.45MPa),并在使用过程中承受压力。此外,水凝胶复合材料显示出良好的生物相容性。在大鼠致死性股动脉损伤中的体内应用表明,水凝胶复合材料的止血时间(2.5 分钟)明显快于商业 Celox(3.3 分钟)和纱布(4.6 分钟),并且很容易从伤口中去除。辐照后的复合材料在 1.5 年内保持稳定。因此,水凝胶复合材料具有作为快速局部止血剂的应用潜力。