Geelhoed W J, van der Bogt K E A, Rothuizen T C, Damanik F F R, Hamming J F, Mota C D, van Agen M S, de Boer H C, Restrepo M Tobón, Hinz B, Kislaya A, Poelma C, van Zonneveld A J, Rabelink T J, Moroni L, Rotmans J I
Department of Internal Medicine, Leiden University Medical Center, the Netherlands; Einthoven Laboratory of Vascular and Regenerative Medicine, the Netherlands.
Department of Surgery, Leiden University Medical Center, the Netherlands.
Biomaterials. 2020 Jan;229:119577. doi: 10.1016/j.biomaterials.2019.119577. Epub 2019 Oct 29.
The durability of prosthetic arteriovenous (AV) grafts for hemodialysis access is low, predominantly due to stenotic lesions in the venous outflow tract and infectious complications. Tissue engineered blood vessels (TEBVs) might offer a tailor-made autologous alternative for prosthetic grafts. We have designed a method in which TEBVs are grown in vivo, by utilizing the foreign body response to subcutaneously implanted polymeric rods in goats, resulting in the formation of an autologous fibrocellular tissue capsule (TC). One month after implantation, the polymeric rod is extracted, whereupon TCs (length 6 cm, diameter 6.8 mm) were grafted as arteriovenous conduit between the carotid artery and jugular vein of the same goats. At time of grafting, the TCs were shown to have sufficient mechanical strength in terms of bursting pressure (2382 ± 129 mmHg), and suture retention strength (SRS: 1.97 ± 0.49 N). The AV grafts were harvested at 1 or 2 months after grafting. In an ex vivo whole blood perfusion system, the lumen of the vascular grafts was shown to be less thrombogenic compared to the initial TCs and ePTFE grafts. At 8 weeks after grafting, the entire graft was covered with an endothelial layer and abundant elastin expression was present throughout the graft. Patency at 1 and 2 months was comparable with ePTFE AV-grafts. In conclusion, we demonstrate the remodeling capacity of cellularized in vivo engineered TEBVs, and their potential as autologous alternative for prosthetic vascular grafts.
用于血液透析通路的人工动静脉（AV）移植物耐久性较低，主要原因是静脉流出道的狭窄病变和感染并发症。组织工程血管（TEBVs）可能为人工移植物提供定制的自体替代物。我们设计了一种方法，通过利用山羊对皮下植入聚合物棒的异物反应，使TEBVs在体内生长，从而形成自体纤维细胞组织囊（TC）。植入后1个月，取出聚合物棒，然后将TC（长度6厘米，直径6.8毫米）作为动静脉导管移植到同一只山羊的颈动脉和颈静脉之间。在移植时，TC在破裂压力（2382±129毫米汞柱）和缝线保留强度（SRS：1.97±0.49牛）方面显示出足够的机械强度。AV移植物在移植后1或2个月收获。在体外全血灌注系统中，与初始TC和ePTFE移植物相比，血管移植物的管腔显示出较低的血栓形成倾向。移植后8周，整个移植物被内皮细胞层覆盖，移植物中存在丰富的弹性蛋白表达。1个月和2个月时的通畅率与ePTFE AV移植物相当。总之，我们证明了体内工程化的细胞化TEBVs的重塑能力及其作为人工血管移植物自体替代物的潜力。
