Insulin therapy maintains the performance of PVA-coated PCL grafts in a diabetic rat model
Insulin therapy maintains the performance of PVA-coated PCL grafts in a diabetic rat model
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胰岛素治疗可维持糖尿病大鼠模型中 PVA 涂层 PCL 移植物的性能
DOI：
10.1039/d2bm00531j
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发表时间：
2022
影响因子：
6.6
通讯作者：
Hiroyuki Kamiya
中科院分区：
文献类型：
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作者：
Yuta Kikuchi;Kyohei Oyama;Takumi Yoshida;Daisuke Naruse;Masahiro Tsutsui;Shingo Kunioka;Naohiro Wakabayashi;Hiroyuki Kamiya
血管组织工程已经在“健康”动物模型中显示出有希望的结果。然而，关于人工移植物在“病理条件”下的功效的研究是有限的。因此，在本研究中，我们旨在表征聚乙烯醇（PVA）涂层聚-ε-己内酯（PCL）移植物（PVA-PCL移植物）在糖尿病条件下的性能。为此，PCL移植物通过静电纺丝产生并涂覆有亲水性PVA聚合物，同时通过链脲佐菌素注射建立糖尿病大鼠模型（DM）。此后，在体内评价移植物在大鼠肾下腹主动脉中的性能。因此，我们观察到健康组在移植物管腔中显示CD 31阳性/αSM阳性细胞。此外，PVA-PCL移植物的通畅率在2周时为100%（n = 7），而所有DM大鼠（n = 8）显示出闭塞的移植物。然而，用中性鱼精蛋白哈格多恩胰岛素（tDM）治疗DM大鼠显著改善了通畅率（100%; n = 5）。此外，2周时，tDM组对应的内膜覆盖率与健康组相当（tDM vs.健康组：16.1% vs. 14.7%，p = 0.931）。因此，本研究表明，PVA-PCL移植物的性能在DM大鼠中受损;然而，胰岛素治疗逆转了这种损害。这些发现强调了使用与临床实践中遇到的病例更相似的模型以获得临床适用的小直径血管移植物的重要性。
Vascular tissue engineering has shown promising results in “healthy” animal models. However, studies on the efficacy of artificial grafts under “pathological conditions” are limited. Therefore, in this study, we aimed to characterize the performance of polyvinyl alcohol (PVA)-coated poly-ε-caprolactone (PCL) grafts (PVA-PCL grafts) under diabetic conditions. To this end, PCL grafts were produced via electrospinning and coated with the hydrophilic PVA polymer, while a diabetic rat model (DM) was established via streptozotocin injection. Thereafter, the performance of the graft in the infrarenal abdominal aorta of the rats was evaluated in vivo. Thus, we observed that the healthy group showed CD31 positive/αSM positive cells in the graft lumen. Further, the patency rate of the PVA-PCL graft was 100% at 2 weeks (n = 7), while all the DM rats (n = 8) showed occluded grafts. However, the treatment of DM rats with neutral protamine Hagedorn insulin (tDM) significantly improved the patency rate (100%; n = 5). Furthermore, the intimal coverage rate corresponding to the tDM group was comparable to that of the healthy group at 2 weeks (tDM vs. healthy: 16.1% vs. 14.7%, p = 0.931). Therefore, the present study demonstrated that the performance of the PVA-PCL grafts was impaired in DM rats; however, insulin treatment reversed this impairment. These findings highlighted the importance of using a model that more closely resembles the cases that are encountered in clinical practice to achieve a clinically applicable vascular graft with a small diameter.