镍钛形状记忆合金支架再造全耳郭后血管生成动态观察

Dynamic observation of angiogenesis following total auricular reconstruction with nickel-titanium shape memory alloy stent

背景:课题系镍钛记忆合金丝网支架全耳郭再造的系列研究,在动物体内完成的皮肤扩张及支架植入已取得初步成功。目的:观察镍钛记忆合金丝网作为耳再造支架进行全耳郭再造后血管生成情况。设计、时间及地点:随机分组设计,对比观察动物实验。于2004-04/2005-10在复旦大学附属眼耳鼻喉科医院中心实验室、安徽省立医院和复旦大学附属华山医院核医学科完成。材料:新西兰大白兔12只分成皮肤扩张组和未扩张组,每组6只。方法:扩张组先行植入皮肤软组织扩张器皮下扩张后再植入已制成人耳郭形状的镍钛合金丝网作为全耳郭再造的支架,未扩张组则直接皮下植入支架。主要观察指标:采用免疫组织化学方法检测支架植入后1,3,6,9,12个月的血管内皮生长因子、CD31的表达;利用放射性核素99Tcm-PYP动态观察支架植入后1,3,6,9,12个月支架植入处局部新生血管增加的变化情况。结果:连续观察12个月扩张组5只动物局部生长良好,再造耳郭形态较满意。1只动物于12个月时出现支架外露,再次修补成功。未扩张组未发生支架外露,但外形表现较扩张组差。支架植入后周围组织表达血管内皮生长因子阳性细胞数量和CD31标记的微血管数逐渐增多,3个月达高峰,6个月后数量趋于稳定。支架植入后3个月扩张组明显多于未扩张组(P<0.05)。99Tcm-PYP放射性核素显像显示植入侧与对侧的单位像素放射性计数比值在3个月时最大,超过对侧近50%,而在9个月和12个月时比值接近。结论:镍钛形状记忆合金支架植入皮下可以顺利完成纤维血管化过程,获得较理想的耳郭外观形态效果;通过放射性核素显像技术可以动态观察血管生成的过程。

BACKGROUND： The subject is a part of research series of nickel-titanium （NiTi） shape alloy stent, which has proved successful in skin expansion and stent implantation in vivo. OBJECTIVE： To observe the angiogenesis following total auricular reconstruction with NiTi shape memory alloy stent in vivo. DESIGN, TIME AND SETTING： The randomized control grouping experiment was performed in the Central Laboratory of EENT Hospital of Fudan University, Anhui Provincial Hospita/and Department of Nuclear Medicine, Huashan Hospital of Fudan University from April 2004 to October 2005. MATERIALS： Twelve New Zealand rabbits were randomized divided into the skin-expanded group and the unexpanded group with 6 in each. METHODS： Each animal underwent subcutaneous implantation with a NiTi alloy framework like human auricle. In the skin-expanded group, the stent was implanted after skin expansion, while no treatment in the unexpanded group. MAIN OUTCOME MEASURES： Vascular endothelial growth factor （VEGF）, expression of CD31 and changes of implant vascularization were detected by immunohistochemistry staining and radionuclide ^99Tc^m-PYP at 1, 3, 6, 9, 12 months after implantation, respectively. RESULTS： One rabbit had exposure of the NiTi alloy stent which was then repaired. All the other rabbits tolerated the implants well, and there were no complications in the skin-expanded group by 12 months observation. Though there wasno exposure in the unexpanded group, the external appearance of auricle was not as well as in the other group. The amount of VEGF-positive cells and CD31 marked microvessel density count were gradually increased, reached the peak at 3 months, and stabilized at 6 months. Compared with the unexpanded group, the cell population was significantly greater in the skin-expanded group at 3 months （P 〈 0.05）. ^99Tc^m-PYP radionuclide imaging showed that the activity ratio of radioactive counting in the placement region was greatest at 3 month, which 50% greater than that in the contralateral region, while the ratio was approximated at 9 and 12 months. CONCLUSION： NiTi shape memory alloy stent can smoothly pass：the process of fibrovascularization and obtain ideal appearance of auricle, which process can be evaluated by radionuclide imaging technique.