构建肝素控释的介孔小口径人工血管的研究

Experimental research on the novel small-caliber vascular prosthesis basing on controlled release ofheparin from mesoporous channel

目的制备负载肝素的介孔膨体聚四氟乙烯（eFFFE）人工血管并观察其生物相容性。方法实验分为介孔人工血管组和普通人工血管组。制备不同性能的固载肝素的介孔人工血管，标记为HMVP．n（n=1，2，3）。利用凝血酶失活实验、加压灌注实验、蛋白吸附实验和乳酸脱氢酶（LDH）细胞毒性实验进行检测。结果成功制备出固载肝素的介孔人工血管。凝血酶失活实验显示：HMBVP．n在分别释放5d和20d后仍能灭活大部分凝血酶，HMBVP-1能保持更好的肝素释放性能（P〈0．05）。加压灌注实验显示合成血管无明显直径和长度的变化（P〉0．05），HMVP-n纤维蛋白的吸附值（OD值）分别为0．29±0．12、0．31±0．06、0．30±0．07，较对照组（0．56±0．23）明显地减少了吸附量（P〈0．05），而白蛋白在HMVP-n人工血管吸附的OD值分别为0．390±0．150、0．327±0．210、0．332±0．240，较对照组（0．291±0．220）更易于白蛋白的吸附（P〈0．05），其中HMVP-1最为明显，差异有统计学意义（P〈0．05）。细胞毒性实验显示合成血管LDH的吸光度值分别为0．541±0．008、0．583±0．012、0．587±0．009，与对照组（0．624±0．011）比较差异无统计学意义（P〉0．05）。结论肝素固载的含介孔人工血管具有良好的长期抗凝性和生物相容性。

Objective To fabricate the mesoporous-based heparin-loaded expanded polytetraflu oroethylene （ePTFE） vascular prosthesis and evaluate their biocompatibility. Methods The study includ- ed the mesoporous-based vascular prosthesis group and the control group. The chromogenic assay. Press- ing-peffusion test, protein adsorption assay and lactate dehydrogenase （LDH） cytotoxieity assay were deter- mined to evaluate hemoeompatibility and compatibility of vascular prosthesis. Results The heparin-re leased mesoporous-based vascular prosthesis weas synthesized successfully. Tile chromogenic assay con finned that heparin-loaded keep lasting activity than the control vascular prosthesis group （ P 〈 0. 05 ）. HMVP-n keep compliance of original vascular prosthesis （ P 〉 0. 05 ）. The adsorption of fibrinogen on the surface of HMVP-n membranes is effectively reduced （OD values：0. 29 ±0. 12, 0. 31 ±0. 06 and 0. 30± 0. 07, respectively） , but HMVP-n grafts attracted higher amount of albumin （ OD values： 0. 390 ±0. 150, 0. 327 ±0. 210 and 0. 332±0. 240, respectively） compared than unmodified ePTFE graft （ P 〈 0. 05 ）, HMVP-1 especially, there was not significant difference of A values between HMVP-n and unmodified ma terial （P 〉 0. 05 ） by LDH Cytotoxicity Assay. Conclusion The heparin-released mesoporous-based vas cular prosthesis keep lasting antithrombotie activity and has Rood biocompatibilitv.