纳米APS外膜肝素化内膜小口径组织工程血管的实验研究  

Study of tissue-engineered small vascular graft sheathed with nano poly(1,3-diamino-2-hydroxypropaneco-polyolsebacate) on adventitia and coated with heparin on intima

作　　者：刘俊[1] 张晓膺[1] LIU Jun ZHANG Xiao-ying(Department of Cardiothoracic Surgery, Third Affiliated Hospital, Soochow University, Changzhou 213003, China)

机构地区：[1]苏州大学附属第三医院心胸外科,常州213003

出　　处：《上海交通大学学报（医学版）》2017年第3期337-343,共7页Journal of Shanghai Jiao tong University:Medical Science

摘　　要：目的·制备具有良好抗张强度及组织相容性的复合型组织工程血管(HTEV)。方法·制备大鼠脱细胞主动脉血管支架,采用静电纺丝(ES)技术在脱细胞血管支架外覆以纳米氨基醇聚癸二酸甘油酯(APS),使用肝素修饰血管支架内膜,制成HTEV。行HTEV体内植入和功能评价,建立同种异体的大鼠腹主动脉移植模型。移植后6周行血管超声和CT血管造影检查。结果·大鼠主动脉经脱细胞处理后,细胞成分几乎被完全去除,脱细胞组的总DNA含量[(115.4±10.9)ng/mg]相较未脱细胞组[(398.6±14.6)ng/mg]显著下降(P=0.000),但脱细胞对于胶原纤维以及弹力纤维造成损伤。ES-APS包覆后增强了HTEV支架的机械性能,支架壁厚(187±11)μm、缝合强度为(0.51±0.06)N、爆破压力为(2 103±232)mm Hg,均较脱细胞血管显著提高(均P<0.01)。HTEV内膜经肝素修饰后具有较强的抗血小板黏附作用。大鼠异体血管移植后6周检查发现,HTEV通畅性良好,包覆ES-APS能防止扩张和动脉瘤形成。结论·通过在大鼠脱细胞主动脉血管支架外覆以ES-APS,内膜以肝素修饰,成功制备了HTEV,大大提高了抗张强度及组织相容性。Objective · To develop a new hybrid tissue-engineered vascular graft （HTEV） with excellent mechanical properties and biological functions. Methods · Decellularized rat aortas （DRAs） were prepared. Then, electrospinning nano poly （1,3-diamino-2-hydroxypropane-co-polyolsebacate） （ES-APS） was used to sheathe DRAs in order to improve the mechanical properties. After that, the intima of HTEV scaffold was modified with heparin coating. HTEVs were implanted in rat models in vivo to evaluate their biological functions. Six weeks later, vascular ultrasound and micro-CT angiography were carried out. Results · The donor aortic vessels were successfully decellularized. The total DNA content of DRA group [（115.4±10.9） ng/mg] significantly decreased compared with natural aorta group [（398.6±14.6） ng/mg] （P=0.000）. But collagenous fibers and elastic fibers of decellularized vessels were severely injured. Mechanical tests of scaffolds showed that ES-APS significantly enhanced the mechanical properties. The wall thickness [（187±11） μm], suture retention strength [（0.51±0.06） N] and burst pressure [（2 103±232） mmHg] of HTEV group all significantly increased compared with DRA group （P〈0.01）. Heparin coating modification of HTEV significantly reduced the number of adhesive platelets. Vascular ultrasound and micro-CT angiography showed all grafts were totally patent 6 weeks after implantation in rat models. ES-APS sheath successfully prevented the occurrence of vasodilation and aneurysm formation. Conclusion · DRA sheathed with ES-APS on adventitia and coated with heparin on intima is a new kind of HTEV, which possesses increased tensile strength and improved biocompatibility.

关 键 词：组织工程血管 脱细胞 静电纺丝 氨基醇聚癸二酸甘油酯 肝素涂层 

分 类 号：R318.11[医药卫生—生物医学工程]