Development and evaluation of in vivo tissue engineered blood vessels in a porcine model
Development and evaluation of in vivo tissue engineered blood vessels in a porcine model
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DOI：
10.1016/j.biomaterials.2015.10.023
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发表时间：
2016-01-01
期刊：
影响因子：
14
通讯作者：
Rotmans, Joris I.
中科院分区：
文献类型：
--
作者：
Rothuizen, Tonia C.;Damanik, Febriyani F. R.;Rotmans, Joris I.
背景：临床上对新型血管移植物的需求很大。组织工程化血管（TEBV）具有极大的潜力，以改善血管移植手术的结果。在这里，我们提出了一种新的方法，在体内产生自体TEBV。聚合物棒被设计和植入，引起炎症反应，最终被纤维细胞囊包裹。我们假设，挤压后的棒，纤维细胞囊分化成一个足够的血管管道，一旦移植到vasculations.Methods和结果：棒皮下植入猪。4周后，收获具有在其周围生长的组织囊的棒。组织囊移植双侧颈动脉间置。通过血管造影术评价1周和4周的通畅性，随后处死猪。采用免疫组织化学、RNA分析和力学测试对移植前后的组织囊进行组织重塑评价。棒被厚的、血管化良好的组织囊包裹，由周向排列的成纤维细胞、胶原蛋白和少量白细胞组成，具有足够的机械强度。1周后通畅率为100%，4周后通畅率为87.5%。移植后，组织囊朝着血管表型重塑。TEBV的基因谱与颈动脉的相似性更高。室壁厚度和α SMA阳性面积显著增加。有趣的是，移植前存在的（肌）成纤维细胞的相当一部分表达平滑肌细胞标志物。虽然白细胞几乎不再存在，但管腔大部分被内皮细胞覆盖。破裂压力保持稳定后grafts.Conclusions：Autoblasts TEBVs在体内创建具有足够的机械强度，使血管移植。移植物在移植后向血管表型分化。(C)2015爱思唯尔有限公司版权所有。
Background: There's a large clinical need for novel vascular grafts. Tissue engineered blood vessels (TEBVs) have great potential to improve the outcome of vascular grafting procedures. Here, we present a novel approach to generate autologous TEBV in vivo. Polymer rods were engineered and implanted, evoking an inflammatory response that culminates in encapsulation by a fibrocellular capsule. We hypothesized that, after extrusion of the rod, the fibrocellular capsule differentiates into an adequate vascular conduit once grafted into the vasculature.Methods and results: Rods were implanted subcutaneously in pigs. After 4 weeks, rods with tissue capsules grown around it were harvested. Tissue capsules were grafted bilaterally as carotid artery interposition. One and 4-week patency were evaluated by angiography whereupon pigs were sacrificed. Tissue capsules before and after grafting were evaluated on tissue remodeling using immunohistochemistry, RNA profiling and mechanical testing. Rods were encapsulated by thick, well-vascularized tissue capsules, composed of circumferentially aligned fibroblasts, collagen and few leukocytes, with adequate mechanical strength. Patency was 100% after 1 week and 87.5% after 4 weeks. After grafting, tissue capsules remodeled towards a vascular phenotype. Gene profiles of TEBVs gained more similarity with carotid artery. Wall thickness and alpha SMA-positive area significantly increased. Interestingly, a substantial portion of (myo)fibroblasts present before grafting expressed smooth muscle cell markers. While leukocytes were hardly present anymore, the lumen was largely covered with endothelial cells. Burst pressure remained stable after grafting.Conclusions: Autologous TEBVs were created in vivo with sufficient mechanical strength enabling vascular grafting. Grafts differentiated towards a vascular phenotype upon grafting. (C) 2015 Elsevier Ltd. All rights reserved.