Heart Research Institute, Newtown, NSW, Australia.
Acta Biomater. 2011 Jan;7(1):295-303. doi: 10.1016/j.actbio.2010.07.022. Epub 2010 Jul 23.
Small-diameter synthetic vascular graft materials fail to match the patency of human tissue conduits used in vascular bypass surgery. The foreign surface retards endothelialization and is highly thrombogenic, while the mismatch in mechanical properties induces intimal hyperplasia. Using recombinant human tropoelastin, we have developed a synthetic vascular conduit for small-diameter applications. We show that tropoelastin enhances endothelial cell attachment (threefold vs. control) and proliferation by 54.7 ± 1.1% (3 days vs. control). Tropoelastin, when presented as a monomer and when cross-linked into synthetic elastin for biomaterials applications, had low thrombogenicity. Activation of the intrinsic pathway of coagulation, measured by plasma clotting time, was reduced for tropoelastin (60.4 ± 8.2% vs. control). Platelet attachment was also reduced compared to collagen. Reductions in platelet interactions were mirrored on cross-linked synthetic elastin scaffolds. Tropoelastin was subsequently incorporated into a synthetic elastin/polycaprolactone conduit with mechanical properties optimized to mimic the human internal mammary artery, including permeability, compliance, elastic modulus and burst pressure. Further, this multilayered conduit presented a synthetic elastin internal lamina to circulating blood and demonstrated suturability and mechanical durability in a small scale rabbit carotid interposition model.
小直径合成血管移植物的通畅性无法与用于血管旁路手术的人体组织导管相匹配。其外表面会阻碍内皮细胞的形成,并且极易引发血栓形成,而机械性能的不匹配则会导致内膜增生。我们使用重组人原弹性蛋白开发了一种用于小直径应用的合成血管移植物。我们发现原弹性蛋白可显著增强内皮细胞的黏附(是对照组的三倍)和增殖(与对照组相比,第 3 天增长 54.7±1.1%)。原弹性蛋白呈单体形式呈现,且交联后可用于生物材料应用时,其血栓形成性较低。通过血浆凝固时间测量,凝血酶固有途径的激活降低了 60.4±8.2%(与对照组相比)。与胶原蛋白相比,血小板黏附也有所减少。交联的合成弹性蛋白支架上的血小板相互作用减少。随后,原弹性蛋白被掺入到具有优化机械性能的合成弹性蛋白/聚己内酯导管中,其性能类似于人体的内乳动脉,包括通透性、顺应性、弹性模量和爆裂压力。此外,这种多层导管将合成弹性蛋白的内层暴露在循环血液中,并在小型兔颈动脉间置模型中证明了其可缝合性和机械耐久性。