Wang Liangyu, Zhong Yuanyuan, Qian Chuntong, Yang Dongzhi, Nie Jun, Ma Guiping
Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Nature Macromolecules, Ministry of Education, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Acta Biomater. 2020 Sep 15;114:193-205. doi: 10.1016/j.actbio.2020.07.043. Epub 2020 Jul 25.
Natural polymer materials have attracted great attention in the field of hemostasis because of their wide range of source, nontoxicity, hydrophilicity, and air permeability. In the present study, two natural polymers composed of carboxymethyl chitosan (CMCS) and sodium carboxymethylcellulose (CMCNa) plus γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH560) that serves as a crosslinking agent were selected to synthesize a capillary-mimicking composite hemostatic (CCK) sponge with a low density, interconnected microchannel architecture, suitable mechanical strength, high resilience, and ultrastrong liquid absorption capacity. The introduction of a large number of hydrophilic carboxymethyl functional groups and the design of capillary-mimicking structures formed by the ice segregation-induced self-assembly (ISISA) process endowed the CCK sponges with an ultrastrong liquid absorption capacity, which significantly enhanced the hemostatic ability of the materials. Both in vivo and in vitro hemostatic experiments confirmed the potential of the CCK sponges to achieve rapid hemostasis. Additionally, cytotoxicity and hemolysis assays showed that the CCK sponges exhibited good biocompatibility and hemocompatibility. The possible hemostatic mechanism was also discussed in this study. In conclusion, the capillary-mimicking hemostatic sponge exhibits a high potential to induce rapid hemostasis in prehospital emergency and clinical settings. STATEMENT OF SIGNIFICANCE: In the present study, an oriented composite hemostatic (CCK) sponge with a capillary-mimicking structure formed by the ice segregation-induced self-assembly (ISISA) process was designed and used to achieve rapid hemostasis. The unique aligned microchannel structure of the sponge exhibited an ultrastrong capillary-mimicking action and endowed the prepared CCK hemostatic sponge with a strong liquid absorption capacity. By changing the proportion of raw materials, we could modify the unique capillary-mimicking structure with aligned microchannels. Two natural polymer-based materials with abundant hydrophilic groups were chosen to prepare the CCK sponge to fully utilize the characteristics of this structure. The oriented natural polymer-based porous sponge with capillary-mimicking microchannels exhibited a strong hemostatic ability in both in vivo and in vitro tests. The results showed that the CCK sponge with the capillary-mimicking structure has a high potential to achieve rapid hemostasis.
天然高分子材料因其来源广泛、无毒、亲水性和透气性等特点，在止血领域备受关注。在本研究中，选择了两种由羧甲基壳聚糖（CMCS）和羧甲基纤维素钠（CMCNa）以及用作交联剂的γ-(2,3-环氧丙氧基)丙基三甲氧基硅烷（KH560）组成的天然聚合物，合成了一种具有低密度、相互连接的微通道结构、合适的机械强度、高弹性和超强液体吸收能力的仿毛细血管复合止血（CCK）海绵。大量亲水性羧甲基官能团的引入以及通过析冰诱导自组装（ISISA）过程形成的仿毛细血管结构的设计，赋予了CCK海绵超强的液体吸收能力，显著增强了材料的止血能力。体内和体外止血实验均证实了CCK海绵实现快速止血的潜力。此外，细胞毒性和溶血试验表明，CCK海绵具有良好的生物相容性和血液相容性。本研究还探讨了可能的止血机制。总之，仿毛细血管止血海绵在院前急救和临床环境中具有诱导快速止血的高潜力。
在本研究中，设计了一种通过析冰诱导自组装（ISISA）过程形成仿毛细血管结构的定向复合止血（CCK）海绵，用于实现快速止血。海绵独特的排列微通道结构表现出超强的仿毛细血管作用，赋予制备的CCK止血海绵强大的液体吸收能力。通过改变原材料比例，可以改变具有排列微通道的独特仿毛细血管结构。选择两种具有丰富亲水基团的天然聚合物基材料制备CCK海绵，以充分利用这种结构的特性。具有仿毛细血管微通道的定向天然聚合物基多孔海绵在体内和体外试验中均表现出强大的止血能力。结果表明，具有仿毛细血管结构的CCK海绵具有实现快速止血的高潜力。
