Degradation and hemostatic properties of polyphosphate coacervates
Degradation and hemostatic properties of polyphosphate coacervates
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DOI：
10.1016/j.actbio.2016.06.002
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发表时间：
2016-09-01
影响因子：
9.7
通讯作者：
Filiaggi, Mark Joseph
中科院分区：
文献类型：
--
作者：
Momeni, Arash;Filiaggi, Mark Joseph
聚磷酸钠是一种由磷酸单元通过共享氧原子连接在一起而形成的线性聚合物。在聚磷酸钠溶液中加入钙会导致相分离并形成聚磷酸钠凝聚体，这是一种富含聚合物的粘弹性材料。基于其与不同阳离子结合和装载药物的能力，聚磷酸盐凝聚体是一种有趣的候选生物材料。本文综合评价了聚磷酸盐凝聚体的体外降解和止血性能。我们发现聚磷酸盐凝聚体降解和溶解速度很快，一周内失去一半的原始质量，4周后主要转化为焦磷酸盐。短链聚磷酸酯制备的凝聚体的破裂溶解阶段发生得较早，但总体而言，使用较长的聚磷酸酯链并不能显著提高凝聚体的寿命。用Sr或Ba取代Ca不会影响凝聚体的水解，但会减缓它们在介质中的溶解。在全血凝血试验中，凝块显著缩短凝血时间，特别是当使用长链多磷酸盐时。与对照组相比，凝聚链长度和二价阳离子类型显著影响凝血酶原时间和凝血活酶时间，但没有观察到明显的趋势。血小板大量粘附在凝聚体上，特别是那些含有长链多磷酸盐的凝聚体，但观察到的细胞形态表明它们可能没有被完全激活。总之，长链聚磷酸酯凝聚物作为一种可吸收的止血剂具有很大的潜力。
Sodium polyphosphate is a linear polymer formed from phosphate units linked together by sharing oxygen atoms. Addition of calcium to a solution of sodium polyphosphate results in phase separation and formation of a polyphosphate coacervate best described as a polymeric rich viscoelastic material. Polyphosphate coacervate is an interesting candidate as a biomaterial based on its ability to bind with different cations and to be loaded with drugs. Here, in vitro degradation and hemostatic properties of polyphosphate coacervates are comprehensively evaluated. We show that polyphosphate coacervates degrade and dissolve at a fast rate, losing half of their original mass in a week and transforming to mainly pyrophosphate after 4 weeks. This burst dissolution phase happens earlier for the coacervate prepared from very short chain polyphosphate but overall using longer polyphosphate chains does not increase the coacervate longevity significantly. Substitution of Ca with Sr or Ba does not affect the hydrolysis of coacervates but slows down their dissolution into the media. In a whole blood clotting assay, coacervates profoundly decrease the clotting time especially when very long chain polyphosphates are used. While coacervate chain length and divalent cation type were found to significantly affect prothrombin time and thromboplastin time compared to the control, no discernible trends were observed. Platelets adhere in large numbers to coacervates, especially those containing long chain polyphosphate, but the cell morphology observed suggests that they might not to be fully activated. Overall, the long chain polyphosphate coacervate holds a great potential as a resorbable hemostatic agent.