The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta GA 30332.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.
Nat Mater. 2014 Dec;13(12):1108-1114. doi: 10.1038/nmat4066. Epub 2014 Sep 7.
Efforts to create platelet-like structures for the augmentation of haemostasis have focused solely on recapitulating aspects of platelet adhesion; more complex platelet behaviours such as clot contraction are assumed to be inaccessible to synthetic systems. Here, we report the creation of fully synthetic platelet-like particles (PLPs) that augment clotting in vitro under physiological flow conditions and achieve wound-triggered haemostasis and decreased bleeding times in vivo in a traumatic injury model. PLPs were synthesized by combining highly deformable microgel particles with molecular-recognition motifs identified through directed evolution. In vitro and in silico analyses demonstrate that PLPs actively collapse fibrin networks, an emergent behaviour that mimics in vivo clot contraction. Mechanistically, clot collapse is intimately linked to the unique deformability and affinity of PLPs for fibrin fibres, as evidenced by dissipative particle dynamics simulations. Our findings should inform the future design of a broader class of dynamic, biosynthetic composite materials.
人们一直致力于创造类似于血小板的结构来增强止血功能,这些研究仅专注于模仿血小板黏附的某些方面;而对于更复杂的血小板行为,如血栓收缩,则认为这些行为是无法通过合成系统来实现的。在这里,我们报告了完全合成的类似于血小板的颗粒(PLP)的创造,这些颗粒在生理流动条件下增强了体外的凝血,并在创伤性损伤模型中实现了伤口触发的止血和减少出血时间。PLP 是通过将高变形性微凝胶颗粒与通过定向进化识别的分子识别基序结合而合成的。体外和计算机模拟分析表明,PLP 可主动破坏纤维蛋白网络,这是一种类似于体内血栓收缩的新兴行为。从机制上讲,血栓收缩与 PLP 对纤维蛋白纤维的独特变形能力和亲和力密切相关,这一点可以通过耗散粒子动力学模拟来证明。我们的研究结果应该为更广泛的动态生物合成复合材料的设计提供信息。