Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, Kemerovo 650002, Russia.
Laboratory of Organic Synthesis, Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Int J Mol Sci. 2023 May 10;24(10):8540. doi: 10.3390/ijms24108540.
The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility. We then compared the long-term patency and remodeling features of PCL and PHBV/PCL prostheses in a sheep carotid artery interposition model. The research findings verified that the drug coating of both types of prostheses improved their hemocompatibility and tensile strength. The 6-month primary patency of the PCL/Ilo/A prostheses was 50%, while all PHBV/PCL/Ilo/A implants were occluded at the same time point. The PCL/Ilo/A prostheses were completely endothelialized, in contrast to the PHBV/PCL/Ilo/A conduits, which had no endothelial cells on the inner layer. The polymeric material of both prostheses degraded and was replaced with neotissue containing smooth-muscle cells; macrophages; proteins of the extracellular matrix such as type I, III, and IV collagens; and vasa vasorum. Thus, the biodegradable PCL/Ilo/A prostheses demonstrate better regenerative potential than PHBV/PCL-based implants and are more suitable for clinical use.
缺乏合适的自体移植物和无法使用合成假体进行小动脉重建,使得开发替代的有效血管移植物成为必要。在这项研究中,我们制备了负载伊洛前列素(前列环素类似物)的电纺可生物降解聚(ε-己内酯)(PCL)假体和聚(3-羟基丁酸-co-3-羟基戊酸)/聚(ε-己内酯)(PHBV/PCL)假体作为抗血栓药物和具有抗菌活性的阳离子两亲物。我们从药物释放、机械性能和血液相容性等方面对假体进行了表征。然后,我们在绵羊颈动脉间置模型中比较了 PCL 和 PHBV/PCL 假体的长期通畅率和重塑特征。研究结果证实,两种类型假体的药物涂层均提高了其血液相容性和拉伸强度。PCL/Ilo/A 假体的 6 个月原发性通畅率为 50%,而所有 PHBV/PCL/Ilo/A 植入物在同一时间点均闭塞。PCL/Ilo/A 假体完全内皮化,而 PHBV/PCL/Ilo/A 导管则在内层没有内皮细胞。两种假体的聚合物材料降解并被含有平滑肌细胞、巨噬细胞、细胞外基质蛋白(如 I 型、III 型和 IV 型胶原蛋白)和血管周细胞的新生组织取代。因此,可生物降解的 PCL/Ilo/A 假体比基于 PHBV/PCL 的植入物具有更好的再生潜力,更适合临床应用。