Results of preclinical trials in a sheep model of biodegradable small-diameter vascular grafts

L. Antonova, E. Krivkina, M. Khanova, E. Velikanova, V. Matveeva, А. V. Mironov, A. Shabaev, Е. A. Senokosova, T. V. Glushkova, M. Sinitsky, R. Mukhamadiyarov, L. Barbarash
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引用次数: 1

Abstract

Surface modification of polymer vascular matrices is a promising development for preventing vascular graft thrombosis, improving long-term patency and accelerating remodeling. Objective: to study the outcomes of long-term patency of PHBV/PCL/GFmix grafts with iloprost (Ilo) and heparin (Hep) implanted into the carotid artery of sheep. Materials and methods. Matrices 04 mm were fabricated by electrospinning from a polymer composition of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(s-caprolactone) (PCL) with incorporation of endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and chemoattractant molecule (SDF-1a). The fabricated matrices were then modified with Ilo and Hep by complexation via polyvinylpyrrolidone (PVP). Synthetic Gore-Tex grafts were used as a comparison group. The physical and mechanical properties of the studied matrix groups were evaluated, the surface structure of vascular grafts before and after implantation was assessed. Vascular grafts were implanted into the carotid artery of a sheep. The explanted samples were studied via histological and immunofluorescence analysis, the elemental composition of the obtained vascular graft samples was also assessed, and the gene expression profile was evaluated. Results. One day after implantation, the patency of PHBV/PCL/GFmixHep/n° vascular grafts was 62.5%, whereas synthetic Gore-Tex grafts had thrombosis in 100% of cases. At the same time, after 18 months of implantation, the patency of biodegradable PHBV/PCL/GFmixHep/n° vascular grafts decreased to 50%. Permeable drug-coated polymer grafts were completely reabsorbed after 18 months of implantation, and aneurysmally dilated newly-formed vascular tissue was formed in their place. Conclusion. Modification of the surface of PHBV/PCL/GFmix polymer grafts with Hep + Ilo coating improved long-term patency outcomes compared to synthetic Gore-Tex grafts.
可生物降解小直径血管移植羊模型临床前试验结果
高分子血管基质的表面修饰在预防移植物血栓形成、改善血管长期通畅和加速血管重构等方面具有广阔的应用前景。目的:研究伊洛前列素(Ilo)、肝素(Hep)联合PHBV/PCL/GFmix移植羊颈动脉长期通畅的效果。材料和方法。以聚3-羟基丁酸-co-3-羟基戊酸酯(PHBV)和聚s-己内酯(PCL)为原料,加入内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和化学引诱分子(SDF-1a),采用静电纺丝法制备了直径为04 mm的基质。然后用聚乙烯吡咯烷酮(PVP)络合对制备的基质进行Ilo和Hep修饰。合成Gore-Tex移植物作为对照组。评价基质组的物理力学性能,评价血管移植前后的表面结构。血管移植物被植入一只羊的颈动脉。对外植体进行组织学和免疫荧光分析,对获得的血管移植物样本进行元素组成评估,并对基因表达谱进行评估。结果。植入后1天,PHBV/PCL/GFmixHep/n°血管移植物的通畅率为62.5%,而合成Gore-Tex移植物的血栓发生率为100%。同时,植入18个月后,可生物降解的PHBV/PCL/GFmixHep/n°血管移植物的通畅度下降到50%。可渗透的药物包覆聚合物移植物在植入18个月后被完全重新吸收,动脉瘤样扩张的新血管组织在其位置形成。结论。用Hep + Ilo涂层修饰PHBV/PCL/GFmix聚合物接枝的表面,与合成Gore-Tex接枝相比,改善了长期通畅的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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