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载有泼尼松的聚(己内酯-丙交酯)血管外鞘用于提高静脉移植物通畅率

Poly (-Caprolactone--l,l-Lactide) Vascular External Sheath Carrying Prednisone for Improving Patency Rate of the Vein Graft.

作者信息

Wang Yang, Tao Meihan, Wei Huan, Arslan Ahmad Muhammad, Ma Yizhan, Mao Xiaoyan, Hao Liang, Ao Qiang

机构信息

Department of Tissue Enguneering, School of Intelligent Medicine, China Medical University, Shenyang, China.

Department of Chemistry, School of Forensic Medicine, China Medical University, Shenyang, China.

出版信息

Tissue Eng Part A. 2022 May;28(9-10):394-404. doi: 10.1089/ten.TEA.2021.0118. Epub 2022 Jan 4.

Abstract

Coronary artery bypass graft (CABG) surgery is an impactful treatment for coronary heart disease. Intimal hyperplasia is the central reason for the restenosis of vein grafts (VGs) after CABG. The introduction of external vascular sheaths around VGs can effectively inhibit intimal hyperplasia and ensure the patency of VGs. In this study, the well-known biodegradable copolymer poly (-caprolactone--l,l-lactide) (PLCL) was electrospun into high porosity external sheaths. The prednisone loaded in the PLCL sheath was slowly released during the degradation process of PLCL. Under the combined effects of sheath and prednisone, intimal hyperplasia was inhibited. For the cell experiments, all sheaths show low cytotoxicity to L929 cells at different concentrations at different time intervals. The ultrasonography and histological results showed prominent dilation and intimal hyperplasia of VG without sheath after 2 months of surgery. But there was no dilation in PLCL and PLCL groups. Of note, the prednisone-loaded sheath group exhibited efficacy in inhibiting intimal hyperplasia and ensured graft patency. Impact statement To inhibit intimal hyperplasia after coronary artery bypass graft, the use of external vascular sheaths can prevent vein graft (VG) dilatation, then reduce turbulent blood flow shear stress to vessel wall, and lower the stimulation of shear stress to smooth muscle cells (SMCs), so as to prevent the proliferation and migration of vascular SMC. We provide a biodegradable sheath electrospun by poly (-caprolactone--l,l-lactide) (PLCL) loading prednisone and utilize it around VG in animal models. Vascular ultrasound examinations show strong evidence of vascular patency. The histological alterations of VGs in PLCL group gave a narrower intima layer owing to the inhibition effect of prednisone.

摘要

冠状动脉旁路移植术(CABG)是治疗冠心病的一种有效方法。内膜增生是CABG术后静脉移植物(VG)再狭窄的主要原因。在VG周围引入外部血管鞘可有效抑制内膜增生并确保VG通畅。在本研究中,将著名的可生物降解共聚物聚(-己内酯- -l,l-丙交酯)(PLCL)静电纺丝制成高孔隙率的外部鞘。负载在PLCL鞘中的泼尼松在PLCL降解过程中缓慢释放。在鞘和泼尼松的联合作用下,内膜增生受到抑制。对于细胞实验,所有鞘在不同时间间隔的不同浓度下对L929细胞均显示出低细胞毒性。超声检查和组织学结果显示,术后2个月无鞘的VG出现明显扩张和内膜增生。但PLCL组和PLCL组未出现扩张。值得注意的是,负载泼尼松的鞘组在抑制内膜增生方面表现出疗效并确保了移植物通畅。影响声明为抑制冠状动脉旁路移植术后的内膜增生,使用外部血管鞘可防止静脉移植物(VG)扩张,从而降低血管壁的湍流剪切应力,并减少剪切应力对平滑肌细胞(SMC)的刺激,从而防止血管SMC的增殖和迁移。我们提供了一种由聚(-己内酯- -l,l-丙交酯)(PLCL)负载泼尼松静电纺丝制成的可生物降解鞘,并在动物模型中将其用于VG周围。血管超声检查显示血管通畅的有力证据。由于泼尼松的抑制作用,PLCL组VG的组织学改变显示内膜层更窄。

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