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Design of Carrageenan-Based Heparin-Mimetic Gel Beads as Self-Anticoagulant Hemoperfusion Adsorbents
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-02-09 00:00:00 , DOI: 10.1021/acs.biomac.7b01724
Xin Song 1 , Kang Wang 1 , Cheng-Qiang Tang 1 , Wen-Wen Yang 2 , Wei-Feng Zhao 1, 3 , Chang-Sheng Zhao 1
Affiliation  

The currently used hemoperfusion adsorbents such as activated carbon and ion-exchange resin show dissatisfactory hemocompatibility, and a large dose of injected heparin leads to the increasing cost and the risk of systematic bleeding. Natural polysaccharide adsorbents commonly have good biocompatibility, but their application is restricted by the poor mechanical strength and low content of functional groups. Herein, we developed an efficient, self-anticoagulant and blood compatible hemoperfusion adsorbent by imitating the structure and functional groups of heparin. Carrageenan and poly(acrylic acid) (PAA) cross-linked networks were built up by the combination of phase inversion of carrageenan and post-cross-linking of AA, and the formed dual-network structure endowed the beads with improved mechanical properties and controlled swelling ratios. The beads exhibited low protein adsorption amounts, low hemolysis ratios, low cytotoxicity, and suppressed complement activation and contact activation levels. Especially, the activated partial thromboplastin time, prothrombin time, and thrombin time of the gel beads were prolonged over 13, 18, and 4 times than those of the control. The self-anticoagulant and biocompatible beads showed good adsorption capacities toward exogenous toxins (560.34 mg/g for heavy metal ions) and endogenous toxins (14.83 mg/g for creatinine, 228.16 mg/g for bilirubin, and 18.15 mg/g for low density lipoprotein (LDL)), thus, highlighting their potential usage for safe and efficient blood purification.

中文翻译:

卡拉胶类肝素模拟凝胶微珠作为自抗凝血液灌流吸附剂的设计

当前使用的血液灌流吸附剂如活性炭和离子交换树脂表现出不令人满意的血液相容性,并且大剂量注射的肝素导致成本增加和系统性出血的风险。天然多糖吸附剂通常具有良好的生物相容性,但由于机械强度差和官能团含量低而限制了它们的应用。在这里,我们通过模仿肝素的结构和功能基团开发了一种高效,自抗凝剂和血液相容性的血液灌流吸附剂。角叉菜胶的相转化和AA的后交联相结合,形成了角叉菜胶和聚丙烯酸(PAA)的交联网络,并且所形成的双网状结构赋予了珠子改善的机械性能和可控性。溶胀率。珠粒显示出低的蛋白质吸附量,低的溶血率,低的细胞毒性,并抑制了补体激活和接触激活水平。尤其是,凝胶珠的活化的部分凝血活酶时间,凝血酶原时间和凝血酶时间比对照的延长了13倍,18倍和4倍。具有自我抗凝和生物相容性的珠粒对外源性毒素(重金属离子为560.34 mg / g)和内源性毒素(肌酐为14.83 mg / g,胆红素为228.16 mg / g,低密度为18.15 mg / g)具有良好的吸附能力。脂蛋白(LDL)),从而突显了其在安全有效地血液净化中的潜在用途。凝胶珠的活化部分凝血活酶时间,凝血酶原时间和凝血酶时间比对照组延长了13倍,18倍和4倍。具有自我抗凝和生物相容性的珠粒对外源毒素(重金属离子为560.34 mg / g)和内源毒素(肌酐为14.83 mg / g,胆红素为228.16 mg / g,低密度为18.15 mg / g)具有良好的吸附能力。脂蛋白(LDL)),从而突显了其在安全有效地血液净化中的潜在用途。凝胶珠的活化部分凝血活酶时间,凝血酶原时间和凝血酶时间比对照组延长了13倍,18倍和4倍。具有自我抗凝和生物相容性的珠粒对外源毒素(重金属离子为560.34 mg / g)和内源毒素(肌酐为14.83 mg / g,胆红素为228.16 mg / g,低密度为18.15 mg / g)具有良好的吸附能力。脂蛋白(LDL)),从而突显了其在安全有效地血液净化中的潜在用途。
更新日期:2018-02-09
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