End-point immobilization of heparin on plasma-treated surface of electrospun polycarbonate-urethane vascular graft.
End-point immobilization of heparin on plasma-treated surface of electrospun polycarbonate-urethane vascular graft.
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DOI：
10.1016/j.actbio.2017.01.012
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发表时间：
2017-03-15
影响因子：
9.7
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Qiu X;Lee BL;Ning X;Murthy N;Dong N;Li S
由于主要是表面血栓形成，小直径合成血管移植物的失败率很高，有效的表面化学改性对于维持移植物的通畅性至关重要。在这项研究中，我们设计了一种小直径的弹性合成血管移植物，具有现成的可用性和抗血栓形成活性。聚碳酸酯-氨基甲酸乙酯（PCU），静电纺丝生产纳米纤维移植物，密切模仿天然血管的结构和机械强度。为了克服在PCU上添加官能团的困难，我们探索了各种表面改性方法，并确定等离子体处理是用官能胺基团修饰接枝表面的最有效方法，随后通过终点固定化将其用于缀合肝素。此外，我们在体外证实，血浆处理和肝素的终点固定的组合表现出最高的表面密度和相应的肝素分子的最高抗血栓形成活性。此外，从使用大鼠颈总动脉吻合模型的体内研究中，我们发现血浆肝素移植物在2周和4周时的通畅率高于血浆对照（未处理）移植物。更重要的是，我们观察到管腔表面更完全的内皮化，排列整齐的单层内皮细胞，以及血管化和周围组织细胞浸润方面更广泛的移植物整合。这项工作证明了静电纺丝PCU作为合成弹性材料制造纳米纤维血管移植物的可行性，以及通过等离子体处理肝素或其他生物活性分子的缀合赋予移植物表面所需功能化的潜力。尽管在球囊血管成形术和传统外科干预方面取得了进展，但血管闭塞仍然是全世界的主要死亡原因。目前，自体移植物是用于治疗血管闭塞性疾病的金标准移植物。然而，许多血管闭塞性疾病患者没有自体血管移植物可用。因此，广泛认识到需要一种容易获得的、功能性的、小直径的血管移植物（内径<6 mm）。这项工作通过开发合成移植物的抗血栓形成修饰的方法来解决这一关键需求。
Small-diameter synthetic vascular grafts have high failure rate due to primarily surface thrombogenicity, and effective surface chemical modification is critical to maintain the patency of the grafts. In this study, we engineered a small-diameter, elastic synthetic vascular graft with off-the-shelf availability and anti-thrombogenic activity. Polycarbonate-urethane (PCU), was electrospun to produce nanofibrous grafts that closely mimicked a native blood vessel in terms of structural and mechanical strength. To overcome the difficulty of adding functional groups to PCU, we explored various surface modification methods, and determined that plasma treatment was the most effective method to modify the graft surface with functional amine groups, which were subsequently employed to conjugate heparin via end-point immobilization. In addition, we confirmed in vitro that the combination of plasma treatment and end-point immobilization of heparin exhibited the highest surface density and correspondingly the highest anti-thrombogenic activity of heparin molecules. Furthermore, from an in vivo study using a rat common carotid artery anastomosis model, we showed that plasma-heparin grafts had higher patency rate at 2 weeks and 4 weeks compared to plasma-control (untreated) grafts. More importantly, we observed a more complete endothelialization of the luminal surface with an aligned, well-organized monolayer of endothelial cells, as well as more extensive graft integration in terms of vascularization and cell infiltration from the surrounding tissue. This work demonstrates the feasibility of electrospinning PCU as synthetic elastic material to fabricate nanofibrous vascular grafts, as well as the potential to endow desired functionalization to the graft surface via plasma treatment for the conjugation of heparin or other bioactive molecules. Vascular occlusion remains the leading cause of death all over the world, despite advances made in balloon angioplasty and conventional surgical intervention. Currently, autografts are the gold-standard grafts used to treat vascular occlusive disease. However, many patients with vascular occlusive disease do not have autologous vascular graft available. Therefore, there is a widely recognized need for a readily available, functional, small-diameter vascular graft (inner diameter of <6mm). This work addresses this critical need by developing a method of antithrombogenic modification of synthetic grafts.