Qiu Xuefeng, Lee Benjamin Li-Ping, Ning Xinghai, Murthy Niren, Dong Nianguo, Li Song
Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China; Department of Bioengineering, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
Acta Biomater. 2017 Mar 15;51:138-147. doi: 10.1016/j.actbio.2017.01.012. Epub 2017 Jan 6.
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 2weeks and 4weeks 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.
小口径合成血管移植物由于主要存在表面血栓形成性而具有较高的失败率，有效的表面化学修饰对于维持移植物的通畅性至关重要。在本研究中，我们设计了一种具有现货供应和抗血栓形成活性的小口径弹性合成血管移植物。聚碳酸酯-聚氨酯（PCU）通过静电纺丝制备出纳米纤维移植物，其在结构和机械强度方面与天然血管极为相似。为克服向PCU添加官能团的困难，我们探索了各种表面修饰方法，并确定等离子体处理是用功能性胺基团修饰移植物表面的最有效方法，随后通过终点固定法将肝素与之偶联。此外，我们在体外证实，等离子体处理与肝素终点固定相结合表现出最高的表面密度以及相应的肝素分子最高抗血栓形成活性。此外，通过使用大鼠颈总动脉吻合模型的体内研究，我们表明与等离子体对照（未处理）移植物相比，等离子体-肝素移植物在2周和4周时具有更高的通畅率。更重要的是，我们观察到管腔表面有更完整的内皮化，内皮细胞形成排列整齐、组织良好的单层，并且在血管化和周围组织的细胞浸润方面移植物整合更广泛。这项工作证明了将PCU静电纺丝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赋予移植物表面所需功能化以偶联肝素或其他生物活性分子的潜力。
尽管在球囊血管成形术和传统手术干预方面取得了进展，但血管闭塞仍然是全球主要的死亡原因。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，许多患有血管闭塞性疾病的患者没有可用的自体血管移植物。因此，人们广泛认识到需要一种易于获得、功能性强的小口径血管移植物（内径<6mm）。这项工作通过开发一种合成移植物抗血栓形成修饰方法来满足这一关键需求。
