Insulin therapy maintains the performance of PVA-coated PCL grafts in a diabetic rat model

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

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作者:Yuta Kikuchi, Kyohei Oyama, Takumi Yoshida, Daisuke Naruse, Masahiro Tsutsui, Shingo Kunioka, Naohiro Wakabayashi, Hiroyuki Kamiya

Abstract

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.

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