Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Vasc Surg. 2012 Sep;56(3):783-93. doi: 10.1016/j.jvs.2012.02.030.
Tissue-engineered blood vessels (TEBV) have been proposed as an alternative to prosthetic grafts for dialysis access. However, arteriovenous (AV) grafts must withstand extreme flow rates and frequent needle trauma. In a proof-of-concept study, we sought to determine whether scaffold-based TEBV could withstand the hemodynamic and mechanical challenges of chronic dialysis access.
TEBV were constructed using decellularized arterial scaffolds seeded with autologous ovine endothelial cells (EC) derived from circulating endothelial progenitor cells (EPC) using a novel high-affinity capture approach. Seeded scaffolds were preconditioned to arterial pressure and flow in a bioreactor for 2 weeks prior to implantation to create carotid artery to jugular vein AV grafts in each animal. TEBV were healed for 1 month before initiating percutaneous needle puncture 3 days/week. TEBV wall geometry and patency were monitored using duplex imaging and were either explanted for histologic analysis at 2 months (n = 5) or followed for up to 6 months until venous outflow stenosis threatened AV graft patency (n = 6).
Despite high flow, TEBV maintained stable geometry with only modest wall dilation (under 6%) by 4 months after implantation. Needle access was well tolerated with a single puncture site complication, a small pseudoaneurysm, occurring in the late group. Time-to-hemostasis at puncture sites averaged 4 ± 2 minutes. Histologic analysis at 2 months demonstrated repopulation of the outer TEBV wall by host cells and healing of needle punctures by cellular ingrowth and new matrix deposition along the tract. TEBV followed beyond 2 months showed stable wall geometry but, consistent with the primary mode of clinical AV graft failure, all TEBV eventually developed venous anastomotic stenosis (mean, 4.4 ± 0.9 months; range, 3.3-5.6 months postimplantation; n = 6).
This pilot study supports the concept of creating dialysis access from scaffold-based autologous TEBV. Engineered AV grafts were created within a clinically relevant time frame and demonstrated stable wall geometry despite high flow and repeated puncture. Cellular ingrowth and puncture site healing may improve wall durability, but venous outflow stenosis remains the primary mode of TEBV graft failure in the ovine model.
组织工程血管（TEBV）已被提议作为透析通路的人造移植物的替代品。然而，动静脉（AV）移植物必须承受极端的流速和频繁的针创伤。在一项概念验证研究中，我们试图确定基于支架的 TEBV 是否能够承受慢性透析通路的血流动力学和机械挑战。
使用从循环内皮祖细胞（EPC）衍生的自体绵羊内皮细胞（EC）通过一种新的高亲和力捕获方法在脱细胞动脉支架上构建 TEBV。在植入前，将接种的支架在生物反应器中进行动脉压力和血流预适应 2 周，以在每个动物中创建颈动脉至颈静脉 AV 移植物。TEBV 在开始每周 3 天经皮针刺前愈合 1 个月。使用双工成像监测 TEBV 壁几何形状和通畅性，并在 2 个月时（n = 5）进行解剖或在静脉流出狭窄威胁 AV 移植物通畅性时（n = 6）进行长达 6 个月的随访进行组织学分析。
尽管流量很高，但 TEBV 在植入后 4 个月内仍保持稳定的几何形状，仅适度扩张（小于 6%）。经皮穿刺部位并发症耐受性良好，晚期组发生单个穿刺部位并发症，即小假性动脉瘤。穿刺部位止血时间平均为 4 ± 2 分钟。2 个月时的组织学分析显示，宿主细胞重新填充 TEBV 的外壁，细胞向内生长并沿着移植物轨迹新基质沉积愈合针穿刺部位。超过 2 个月的 TEBV 随访显示壁几何形状稳定，但与临床 AV 移植物失败的主要模式一致，所有 TEBV 最终都出现静脉吻合口狭窄（平均 4.4 ± 0.9 个月；范围，植入后 3.3-5.6 个月；n = 6）。
这项初步研究支持使用基于支架的自体 TEBV 构建透析通路的概念。在临床相关时间框架内构建了工程 AV 移植物，尽管流量高且反复穿刺，但仍保持稳定的壁几何形状。细胞向内生长和穿刺部位愈合可能会提高壁的耐久性，但静脉流出狭窄仍然是绵羊模型中 TEBV 移植物失败的主要模式。
