摘要
在血管搭桥和置换手术中,小口径人造血管由于易产生血栓而导致植入早期失败。为了解决小血管的栓塞问题,人们在高分子材料的选择和加工工艺的改进等方面做了大量工作,效果不甚明显,本文针对这一问题的进一步改进做了相关的研究与探索。
本课题将纳米技术、静电纺丝技术、生物医用材料(降解材料和非降解材料)相结合,制备具有自主知识产权、生物相容性好、更接近宿主血管需求的小直径人造血管,用以克服其在移植后易产生血管栓塞的问题。
本课题的研究内容包括对人造小血管制备材料的选择；静电纺装置两方面的改进,一方面对收集滚轴添加波纹化处理装置,另一方面喷丝装置采用双头纺丝；进而进行锥形波纹血管的纺制,选择合理的锥形波纹参数,最后对已选择的人造小血管样品进行生物力学性能测试和细胞培养测试,测试其新型血管的各项性能指标及生物相容性。
采用静电纺丝工艺制备纳米人造小血管,通过双头喷丝装置,制备出直径为5mm的PET/PLLA混纺和在此基础上进行载药的人造小血管。溶剂分别选用氯仿与丙酮(体积比为2：1),三氟乙酸与二氯甲烷(体积比为4：1)的混合溶剂,光敏剂载药量分别为1%,2%,通过性能测试分析得到PET/PLLA的最优参数为：PET的质量分数为10%,PLLA质量分数5%,PET:PLLA=5:5,通过红外分析,PET和PLLA以及二者混纺和光敏剂之间在纳米级条件下,不会发生反应,维持各自的化学物理特性。
通过改造的锥形波纹收集装置制备出锥度和波纹参数不同的锥形波纹人造小血管,可以得出,采用锥形收集滚轴和螺旋波纹处理装置,可使静电纺小口径人造血管在膜剥取过程中容易剥离。可以调节螺旋波纹的螺旋头数和螺旋升角,从而降低血栓形成几率。所制得的人造血管波纹状态连续均匀,且内壁光滑,无阻塞。
最后对之前选出的样品,进行生物力学性能测试和细胞培养测试,可以得出,小直径人造血管的表面螺旋波纹化可以使其弯折性能得到明显改善。锥形波纹人造小血管的弯折性能随着锥角和螺旋头数的增加,而减小。当螺旋头数为4时,可以较好的满足血液稳定流动以及弯折性能的要求。静电纺人造小血管的顺应性还有待进一步的改善。光照和载药量对人造小血管上的细胞生长情况有显著差异。小血管的表面波纹状态对细胞增长有一定的影响,还需进一步探索,以求改善。
利用有限元软件初步模拟血管内血液流动情况,模拟结果显示,锥度角与波纹隔距对血液的速度矢量和压力分布有影响,随着锥度角的增大和波纹隔距的增大,二者指标也越大,为后期动态模拟实验提供了初步方向。
综上所述,本课题成功制备了锥形波纹人造小血管,并通过相关测试对生物相容性和生物力学性能进行检验,为提高小直径人造血管移植通畅率提供了新的方法。
During the surgery of bypass and replacement in vascular, because of thrombosis in small-diameter artificial vascular, which lead to implant failure early. In order to solve the problems of small blood vessels, people do a lot of work in the choice of the polymer materials and the improvement of processing technology, but the effect is not very obvious, therefore, the related research and exploration about the improvement of these problems were done in this paper further.
This subject combines with nanotechnology, electrostatic spinning technology, and biomedical material (degradation of materials and biodegradable materials). Small diameter artificial vascular were prepared with independent intellectual property rights, good biocompatibility and being closer to a host of blood vessel to overcome the restenosis in the blood vessels caused by the transplantation.
This paper refers to the choice of materials of artificial small blood vessel, and the improvement of electrostatic spinning device in two aspects, on the one hand, changing the collection into corrugated and tapered, on the other hand spinning with double injection pumps in the opposite directions and then choose reasonable tapered and corrugated parameters to produce artificial vascular graft,finally to do Biomechanical testing and culture cell on artificial small blood vessel samples, analysing its biocompatibility and various performance indicators of blood vessels.
Using double injection pumps in the opposite directions to spin nanofibers, Produce vascular graft 5mm in diameter with mixed PET and PLLA,drug-loading on which,solvent are chosen with chloroform acetone (volume ratio 2:1), trifluoro ethyl and methylene chloride (volume ratio 4:1) mixed solvents. Through the test analysis of PET/PLLA get the optimal parameters for PET mass ratio is 10%, PLLA mass ratio is 5%, PET:PLLA=5:5, and the analysis of the infrared shows, in the nanoscale conditions, PET,PLLA and drug can not produce chemical reaction, maintaining their characteristics.
Prepare the tapered corrugated artificial small blood vessels with different parameters by the created tapered corrugated collection devices, the conclusion is that the process of taking off the film form the device become easyer than before by the improved collection, which can adjust the helix number and helix angle,so as to reduce the chance thrombosis, besides,the inner surface is smooth and spiral grooves are continuous, which will help blood flow smoothly.
Finally, do biomechanical testing and culture cell on artificial small diameter blood vessel samples,and the conclusion is that the helical corrugation can improve the bending behavior of the vascular graft obviously.With the thread number and taper angle increasing,the bending behavior of the vascular graft get worse.when the thread number is 4,the vascular graft can meet the requirement of which the state of the blood flow can remain stable and the bending behavior of the vascular graft is good, but the compliance small blood vessel compliance remains to be improved.The uviolizing and quantity of drug have a big influnce on the the state of cell growth on the samples. The corrugated state on the surface of the small blood vessel will effect the growth of cells in some extend, which still need to explore further.
Simulate intravascular blood flow situation with the finite element software preliminarily,the simulation results show that the taper Angle and the isolation of blood will influnce corrugated velocity vector and pressure distributionl, with the increase of taper Angle and the increase of the ripples from, the two index become larger,which provides an initial direction for dynamic simulation experiment later.
In summary, the small-diameter tapered and corrugated artificial blood vessel was prepared successfully. And the biomechanical property and the biocompatibility were verified through the relevent experiments. A new approach to improve the patency of small-diameter artificial blood vessel was provided.
引文
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