摘要
目的:改进脂肪族聚氨酯(polyurethane,PU)弹性体表面接枝肝素(heparin,Hep)的工艺过程,观察共价键合法接枝肝素后其血液相容性。方法:实验于2005-08/2006-08于同济大学材料科学与工程学院实验室完成。材料制备:①脂肪族聚氨酯的合成:采用一步法合成以4,4'-甲烷二苯基二异氰酸酯(HMDI)或异氟尔酮二异氰酸醑(IPDI)、扩链剂1,4-丁二醇为硬段,聚四氢呋喃醚为软段的脂肪族聚氨酯,分别生成IPDI型聚氨酯和HMDI型聚氨酯。②共价键合法聚氨酯表面接枝肝素:形成PU-Hep,PU-聚乙烯醇(polyvinylalcohol,PVA)-Hep,PU-聚乙二醇(polyethyleneglycol,PEO)-Hep,PU-PVA-PEO-Hep中间产物。实验评估:①接枝肝素含量的测定:甲苯胺蓝显色法测定聚氨酯表面的肝素含量;甲苯胺蓝分光光度法测定肝素释放速率。②肝素接枝表面的血液相容性测定:通过溶血实验和血小板黏附实验测定。结果:①聚氨酯表面的肝素含量:IPDI型聚氨酯和HMDI型聚氨酯表面肝素(PU-PVA-PEO-Hep)接枝量分别达到64.8,51.0mg/m2。②肝素释放速率:浸泡20d后,IPDI型聚氨酯肝素化表面(PU-PVA-PEO-R-NHCO-Hep)的肝素含量从64.8mg/m2下降到51.7mg/m2(脱落20.2%),HMDI型聚氨酯肝素化表面(PU-PVA-PEO-Hep)的肝素含量从51.0mg/m2下降到39.1mg/m2(脱落23.3%)。肝素的释放速率在浸泡7d后达到稳定,约为0.6×10-8g/(m2·min)。③聚氨酯表面接枝肝素后溶血率:溶血率有一定降低(IPDI型从2.40%降低至1.94%、HMDI型从3.20%降低至2.36%),溶血率均小于5%,符合生物医用材料的溶血性要求,其中IPDI型聚氨酯血液相容性好于HMDI型。④血小板黏附情况:表面改性之前,IPDI型聚氨酯表面黏附的血小板数目多于HMDI型。IPDI型聚氨酯抑制血小板形成血栓的能力好于HMDI型。表面接枝肝素后,PU-PVA-PEO-Hep的血液相容性优于PU-PVA-Hep和PU-PEO-Hep。结论:表面共价键合法接枝肝素的脂肪族聚氨酯有良好的血液相容性,且肝素释放速率慢,基本满足人工心脏瓣膜材料的要求。
AIM： To improve the technique of covalenUy grafting of heparin （Hep） onto the surfaces of acyclic polyurethane （PU） elastomers and to investigate the blood compatibility of Hep-modtfiod PU obtained. METHODS： This experiment was conducted in the laboratory of School of Materials Science and Engineering, Tongji University from August 2005 to August 2006. Material preparation： ①Acyclic PU was synthesized by ＂one-step＂ method, using hexamethylene diisocyanate （HMDI） or isophorone diisocyanate （IPDI） and chain extender, 1,4-butanodiol, as hard segments, while polytetrahydrofuran as soft segment. HMDI-PU and IPDI-PU were obtained, respectively.②Hep was immobilized on the surface of PU elastomers by covalent bond grafting to obtain PU-Hep, PU-polyvinyl alcohol （PVA）-Hep, PU-polyethylene glycol （PEO）-Hep and PU-PVA-PEO-Hep. Experimental evaluation： ①The amount of heparin immobilized on PU surface was determined by toluidine blue colorimetric method and the release rate of heparin was determined by spectrophotometry.② The blood compatibility of heparin immobilized surface was assayed by hemolysis test and platelet adhesion test. RESULTS：① The amounts of heparin grafted on IPDI-PU-PVA-PEO and HMDI-PU-PVA-PEO surfaces were 64.8 mg/m^2 and 51.0 mg/m^2, respectively.②The Hep amount decreased to 51.7 mg/m^2 （released by 20.2%） for IPDI-PU-PVA-PEO-Hep and to 39.1 mg/rn2 （released by 23.3%） for HMDI-PU-PVA-PEO-Hep after 20-day soaking. The release rate of Hep from the heparinized PU became stable after soaked for 7 days and was about 0.6×10^-8 g/（m^2·min）. ③The rate of hemolysis decreased （IPDI-PU from 240% to 1.94%, HMDI-PU from 3.20% to 2.36%） when Hep was immobilized on PU surface. All the rates of hemolysis observed were less than 5%, indicating that the materials prepared met the hemolysis standard of biomedical materials. The blood compatibility of IPDI-PU was better than that of HMDI-PU. ④Platelet adhesion test： The number of adhesive platelet was higher on IPDI-PU than on HMDI-PU, and the ability of inhibiting thrombosis was better. After Hep grafting, the blood compatibility of PU-PVA-PEO-Hep was also superior to that of PU-PVAoHep and PU-PEO-Hep. CONCLUSION： PU surfaces heparinized by covalent bond grafting exhibit good blood compatibility and low release rate of heparin. Such heparin-modified PU can be used as materials for fabricating artificial heart valve.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第13期2415-2419,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
