Degradation and Healing Characteristics of Small-Diameter Poly(ε-Caprolactone) Vascular Grafts in the Rat Systemic Arterial Circulation

Degradation and Healing Characteristics of Small-Diameter Poly(ε-Caprolactone) Vascular Grafts in the Rat Systemic Arterial Circulation
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DOI:
10.1161/circulationaha.108.795732
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发表时间:
2008-12-09
期刊:
影响因子:
37.8
通讯作者:
Walpoth, Beat H.
Walpoth, Beat H.
中科院分区:
医学1区
文献类型:
--
作者:
Pektok, Erman;Nottelet, Benjamin;Walpoth, Beat H.

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背景--传统人工血管的长期通畅率低于6 mm的内径是不能令人满意的。聚己内酯(PCL)是一种具有较长降解时间的可生物降解聚合物。以聚四氟乙烯(EPTFE)为对照,研究PCL纳米纤维制成的小直径血管移植物的体内愈合和降解特性。方法和结果:用PCL(M-n=80000 g/mol)静电纺丝法制备了内径为2 mm的PCL血管移植物。30只大鼠分别植入PCL(n=15)和ePTFE(n=15)。对大鼠进行24周的随访。在随访期结束时,用数字减影血管造影术评价血管的通畅性和结构完整性。取腹主动脉,包括移植物,在光镜下观察。通过计算机组织形态计量学测量内皮覆盖率、新生内膜形成和跨壁细胞生长。所有动物均存活至随访结束,两组移植血管均通畅。数字减影血管造影术显示PCL组无狭窄,但ePTFE组18周时有1个移植物出现狭窄(40%),24周时有1个移植物出现狭窄(50%)。所有移植物均未显示动脉瘤样扩张。PCL组的内皮覆盖率明显好于PCL组。两组间新生内膜形成情况相似。PCL组巨噬细胞和成纤维细胞向内生长,并伴有细胞外基质形成和新生血管形成。12周后,所有标本均可见软骨样化生灶位于PCL移植物的新生内膜中。结论:与ePTFE相比,小直径PCL移植物具有更好的愈合特性,是一种很有前途的移植材料。更快的内皮化和细胞外基质的形成,伴随着移植纤维的降解,似乎是主要的优势。对降解和移植物愈合特性的进一步评估可能会导致这种移植物在临床上用于血运重建过程。(发行量。2008;118:2563-2570。)
Background-Long-term patency of conventional synthetic grafts is unsatisfactory below a 6-mm internal diameter. Poly(epsilon-caprolactone) (PCL) is a promising biodegradable polymer with a longer degradation time. We aimed to evaluate in vivo healing and degradation characteristics of small-diameter vascular grafts made of PCL nanofibers compared with expanded polytetrafluoroethylene (ePTFE) grafts.Methods and Results-We prepared 2-mm-internal diameter grafts by electrospinning using PCL (M-n = 80 000 g/mol). Either PCL (n = 15) or ePTFE (n = 15) grafts were implanted into 30 rats. Rats were followed up for 24 weeks. At the conclusion of the follow-up period, patency and structural integrity were evaluated by digital subtraction angiography. The abdominal aorta, including the graft, was harvested and investigated under light microscopy. Endothelial coverage, neointima formation, and transmural cellular ingrowth were measured by computed histomorphometry. All animals survived until the end of follow-up, and all grafts were patent in both groups. Digital subtraction angiography revealed no stenosis in the PCL group but stenotic lesions in 1 graft at 18 weeks (40%) and in another graft at 24 weeks (50%) in the ePTFE group. None of the grafts showed aneurysmal dilatation. Endothelial coverage was significantly better in the PCL group. Neointimal formation was comparable between the 2 groups. Macrophage and fibroblast ingrowth with extracellular matrix formation and neoangiogenesis were better in the PCL group. After 12 weeks, foci of chondroid metaplasia located in the neointima of PCL grafts were observed in all samples.Conclusions-Small-diameter PCL grafts represent a promising alternative for the future because of their better healing characteristics compared with ePTFE grafts. Faster endothelialization and extracellular matrix formation, accompanied by degradation of graft fibers, seem to be the major advantages. Further evaluation of degradation and graft healing characteristics may potentially lead to the clinical use of such grafts for revascularization procedures. (Circulation. 2008; 118: 2563-2570.)