Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer.
Peptide valency plays an important role in the activity of a synthetic fibrin-crosslinking polymer.
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DOI：
10.1016/j.biomaterials.2017.04.002
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发表时间：
2017-07
期刊：
影响因子：
14
通讯作者：
Pun SH
中科院分区：
文献类型：
--
作者：
Lamm RJ;Lim EB;Weigandt KM;Pozzo LD;White NJ;Pun SH
治疗性聚合物具有提高出血或不受控制的出血标准，作为合成的止血。 pepperides是链接的。必须确定纤维蛋白结合的辣椒对基于甲基丙烯酸甲酯的葡萄糖的控制，以产生肽阀，范围为0至10个，每个聚合物的valens和valens a valens a valens a valens noperness和valos越来越多。坚硬57％，降低了凝块分解与磷酸盐缓冲的盐水相比，有69％的趋势是中子散射的，这探测了在polystat的存在下形成的云的结构。能力体外评估以预测体内效率。
Therapeutic polymers have the potential to improve the standard of care for hemorrhage, or uncontrolled bleeding, as synthetic hemostats. PolySTAT, a fibrin-crosslinking peptide-polymer conjugate, has the capacity to rescue fibrin clot formation and improve survival in a model of acute traumatic bleeding. PolySTAT consists of a synthetic polymer backbone to which targeting fibrin-binding peptides are linked. For translation of PolySTAT, the optimal valency of peptides must be determined. Grafting of fibrin-binding peptides to the poly(hydroxyethyl methacrylate)-based backbone was controlled to produce peptide valencies ranging from 0 to 10 peptides per polymer. PolySTATs with valencies of ≈4 or greater resulted in increased clot firmness, kinetics, and decreased breakdown as measured by thromboelastometry. A valency of ≈4 increased clot firmness 57% and decreased clot breakdown 69% compared to phosphate-buffered saline. This trend was characterized by neutron scattering, which probed the structure of clots formed in the presence of PolySTAT. Finally, PolySTAT with valencies of 4 (100% survival; p = 0.013) and 8 (80% survival; p = 0.063) improved survival compared to an albumin control in a femoral artery injury model (20% survival). This work demonstrates tunability of hemostatic polymers and the ability of in vitro assays to predict in vivo efficacy.