Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation.
Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation.
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DOI：
10.1039/c8tb01582a
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Cancan Xu;A. Kuriakose;Danh Truong;Primana Punnakitikashem;K. Nguyen;Yi Hong
中科院分区：
文献类型：
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作者：
Cancan Xu;A. Kuriakose;Danh Truong;Primana Punnakitikashem;K. Nguyen;Yi Hong
充分和持续的抗血栓性对于血液接触材料至关重要，因为材料表面血小板粘附和活化引起的血液凝固和血栓形成可能导致功能失效，甚至致命的结果。将抗血栓形成部分缀合到聚合物中，而不是表面改性或共混，可以在一段时间内将聚合物的抗血栓形成性保持在高水平。本研究以聚己内酯（PCL）二醇、己二异氰酸酯（HDI）和抗血栓药物双嘧达莫（DPA）为原料，采用一锅一步法合成了一系列无规交联、弹性、可生物降解的聚氨酯（PU-DPA）。所得PU-DPA聚合物的机械性质、亲水性、体外降解和抗血栓形成性可通过改变并入的DPA量来调整。聚氨酯的表面和本体亲水性随着疏水DPA量的增加而降低。所有PU-DPA聚合物均表现出较强的力学性能和良好的弹性。PU-DPA在PBS和脂肪酶/PBS溶液中的降解速率均随DPA含量的增加而降低。与不含DPA的聚氨酯相比，将DPA掺入聚氨酯中的CoCl 2显著降低了血小板粘附和活化，并且还可以实现持续的抗血栓形成。PU-DPA膜也支持人脐静脉内皮细胞的生长。这种抗血栓形成的生物可降解聚氨酯具有吸引人的机械性能、血液相容性和细胞相容性，表明它具有用于血液接触装置和心血管组织修复和再生的巨大潜力。
Sufficient and sustained anti-thrombogenicity is essential for blood-contacting materials, because blood coagulation and thrombosis caused by platelet adhesion and activation on material surfaces may lead to functional failure and even fatal outcomes. Covalently conjugating antithrombogenic moieties into polymer, instead of surface modifying or blending, can maintain the anti-thrombogenicity of polymer at a high level over a time range. In this study, series of randomly crosslinked, elastic, biodegradable polyurethanes (PU-DPA) were synthesized through a one-pot and one-step method from polycaprolactone (PCL) diol, hexamethylene diisocyanate (HDI) and anti-thrombogenic drug, dipyridamole (DPA). The mechanical properties, hydrophilicity, in vitro degradation, and anti-thrombogenicity of the resultant PU-DPA polymers can be tuned by altering the incorporated DPA amount. The surface and bulk hydrophilicity of the polyurethanes decreased with increasing hydrophobic DPA amount. All PU-DPA polymers exhibited strong mechanical properties and good elasticity. The degradation rates of the PU-DPAs decreased with increasing DPA content in both PBS and lipase/PBS solutions. Covalently incorporating DPA into the polyurethane significantly reduced the platelet adhesion and activation compared to the polyurethane without DPA, and also can achieve sustained anti-thrombogenicity. The PU-DPA films also supported the growth of human umbilical vein endothelial cells. The attractive mechanical properties, blood compatibility, and cell compatibility of this anti-thrombogenic biodegradable polyurethane indicate that it has a great potential to be utilized for blood-contacting devices, and cardiovascular tissue repair and regeneration.