Pektok Erman, Nottelet Benjamin, Tille Jean-Christophe, Gurny Robert, Kalangos Afksendiyos, Moeller Michael, Walpoth Beat H
Department of Cardiovascular Surgery, Faculty of Medicine, University Hospital of Geneva, Geneva 14, Switzerland.
Circulation. 2008 Dec 9;118(24):2563-70. doi: 10.1161/CIRCULATIONAHA.108.795732. Epub 2008 Nov 24.
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.
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.
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.
传统合成移植物内径小于6毫米时,其长期通畅性并不理想。聚(ε-己内酯)(PCL)是一种有前景的可生物降解聚合物,降解时间更长。我们旨在评估与膨体聚四氟乙烯(ePTFE)移植物相比,由PCL纳米纤维制成的小直径血管移植物在体内的愈合和降解特性。
我们使用PCL(M(n)=80,000 g/mol)通过静电纺丝制备了内径为2毫米的移植物。将PCL移植物(n=15)或ePTFE移植物(n=15)植入30只大鼠体内。对大鼠进行24周的随访。随访期结束时,通过数字减影血管造影评估通畅性和结构完整性。将包括移植物的腹主动脉取出,在光学显微镜下进行研究。通过计算机组织形态计量学测量内皮覆盖、新生内膜形成和跨壁细胞向内生长情况。所有动物均存活至随访结束,两组所有移植物均保持通畅。数字减影血管造影显示PCL组无狭窄,但ePTFE组在18周时有1个移植物出现狭窄病变(40%),在24周时有另1个移植物出现狭窄病变(50%)。所有移植物均未出现动脉瘤样扩张。PCL组的内皮覆盖明显更好。两组之间新生内膜形成情况相当。PCL组巨噬细胞和成纤维细胞向内生长以及细胞外基质形成和新生血管生成情况更好。12周后,在所有样本中均观察到位于PCL移植物新生内膜中的软骨样化生灶。
小直径PCL移植物因其与ePTFE移植物相比具有更好的愈合特性,代表了未来一种有前景的替代物。更快的内皮化和细胞外基质形成,以及移植物纤维的降解,似乎是主要优势。对降解和移植物愈合特性的进一步评估可能会促使此类移植物在血管重建手术中得到临床应用。