Department of Nephrology, Leiden University Medical Center, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, The Netherlands.
Department of Tissue Regeneration, University Twente, The Netherlands.
Biomaterials. 2016 Jan;75:82-90. doi: 10.1016/j.biomaterials.2015.10.023. Epub 2015 Oct 22.
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.
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 αSMA-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.
Autologous TEBVs were created in vivo with sufficient mechanical strength enabling vascular grafting. Grafts differentiated towards a vascular phenotype upon grafting.
临床上对新型血管移植物有很大的需求。组织工程血管（TEBV）具有改善血管移植手术效果的巨大潜力。在这里，我们提出了一种在体内生成自体 TEBV 的新方法。设计并植入聚合物棒，引发炎症反应，最终被纤维细胞囊包裹。我们假设，在挤出棒后，纤维细胞囊在移植到血管中后会分化为足够的血管管腔。
将棒状物皮下植入猪体内。4 周后，取出周围有组织胶囊生长的棒。将组织胶囊作为颈动脉间置物双侧移植。通过血管造影评估 1 周和 4 周的通畅性，然后处死猪。在移植前后，通过免疫组织化学、RNA 谱分析和力学测试评估组织重塑。棒状物被厚而血管丰富的组织胶囊包裹，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 周后为 87.5%。移植后，组织胶囊向血管表型重塑。TEBV 的基因谱与颈动脉更相似。壁厚度和αSMA 阳性面积显著增加。有趣的是，移植前存在的相当一部分（肌）成纤维细胞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。移植后爆破压保持稳定。
体内成功生成了具有足够机械强度的自体 TEBV，能够进行血管移植。移植后，移植物向血管表型分化。
