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采用核壳纤维结构原位构建小直径组织工程血管移植物及其在大鼠腹主动脉置换模型中的一年评估。

Fabrication of small-diameter in situ tissue engineered vascular grafts with core/shell fibrous structure and a one-year evaluation via rat abdominal vessel replacement model.

机构信息

School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China.

Department of Vascular Surgery, Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China; Department of Vascular Surgery, Tongren Hospital, Capital Medical University, Beijing, China.

出版信息

Biomater Adv. 2024 Dec;165:214018. doi: 10.1016/j.bioadv.2024.214018. Epub 2024 Aug 31.

Abstract

A high vascular patency was realized in the bulk or surface heparinized small-diameter in situ tissue-engineered vascular grafts (TEVGs) via a rabbit carotid artery replacement model in our previous studies. Those surface heparinized TEVGs could reduce the occurrence of aneurysms, but with a low level of the remodeled elastin, whereas those bulk heparinized TEVGs displayed a faster degradation and an increasing occurrence of aneurysms, but with a high level of the regenerated elastin. To combine the advantages of the bulk and surface graft heparinization to boost the remodeling of elastin and defer the occurrence of aneurysms, a coaxial electro-spinning technique was used to fabricate a kind of small-diameter core/shell fibrous structural in situ TEVGs with a faster degradable poly(lactic-co-glycolic acid) (PLGA) as a core layer and a relatively lower degradable poly(ε-caprolactone) (PCL) as a shell layer followed by the surface heparinization. The in vitro mechanical performance and enzymatic degradation tests revealed the resulting PLGA@PCL-Hep in situ TEVGs possessing not only a faster degradation rate, but also the mechanical properties comparable to those of human saphenous veins. After implanted in the rat abdominal aorta for 12 months, the good endothelialization, low inflammation, and no calcification were evidenced. Furthermore, the neointima layer of regenerated new blood vessels was basically constructed with a well-organized arrangement of elastin and collagen proteins. The results showed the great potential of these in situ TEVGs to be used as a novel type of long-term small-diameter vascular grafts.

摘要

在我们之前的研究中,通过兔颈动脉替代模型,实现了大块或表面肝素化小直径原位组织工程血管移植物(TEVG)的高血管通畅率。那些表面肝素化的 TEVG 可以减少动脉瘤的发生,但弹性蛋白的重塑水平较低,而那些大块肝素化的 TEVG 则显示出更快的降解和更高的动脉瘤发生几率,但再生的弹性蛋白水平较高。为了结合大块和表面移植物肝素化的优势,促进弹性蛋白的重塑并延迟动脉瘤的发生,采用同轴静电纺丝技术制造了一种小直径的核心/壳纤维结构原位 TEVG,其快速可降解的聚乳酸-共-羟基乙酸(PLGA)作为芯层,相对较低可降解的聚己内酯(PCL)作为壳层,然后进行表面肝素化。体外机械性能和酶降解试验表明,所得的 PLGA@PCL-Hep 原位 TEVG 不仅具有更快的降解率,而且具有与人股静脉相当的机械性能。在大鼠腹主动脉内植入 12 个月后,证明具有良好的内皮化、低炎症和无钙化。此外,再生新血管的内皮层基本由弹性蛋白和胶原蛋白蛋白的有序排列构成。结果表明,这些原位 TEVG 具有作为新型长期小直径血管移植物的巨大潜力。

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