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一种具有自组装能力的疏水性改性壳聚糖,能够实现可逆的止血作用。

A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action.

机构信息

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.

出版信息

Biomaterials. 2011 May;32(13):3351-7. doi: 10.1016/j.biomaterials.2010.12.033. Epub 2011 Feb 5.

Abstract

Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of α-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis - e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.

摘要

哺乳动物伤口处的血液流失会被迅速形成的止血塞所阻止,即蛋白质纤维蛋白的自组装网络,它会将液态血液局部转化为凝胶状凝块。在这里,我们报告了一种具有类似快速凝胶化血液能力的两亲性生物聚合物;此外,凝胶化所基于的自组装很容易通过引入基于糖的超分子而恢复为液态。该生物聚合物是多糖壳聚糖的疏水改性 (hm) 衍生物。当 hm-壳聚糖与肝素化的人血接触时,它会迅速将液体转化为弹性凝胶。相比之下,天然壳聚糖(没有疏水基团)不会使血液凝固。凝胶化是因为 hm-壳聚糖上的疏水基团插入到血细胞的膜中,从而将细胞连接成一个跨越样本的网络。通过添加具有内部疏水口袋的超分子α-环糊精可以逆转凝胶化:聚合物疏水基团与血细胞分离并嵌入环糊精中,从而破坏细胞网络。我们相信 hm-壳聚糖有可能成为创伤中心和军队使用的有效且低成本的止血敷料。在小动物和大动物损伤模型中的初步测试表明,它在实现止血方面的效果更好,例如,在大鼠模型中,股静脉横断时的出血时间比对照组减少了 90%。

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