Caracciolo Pablo C, Rial-Hermida María Isabel, Montini-Ballarin Florencia, Abraham Gustavo A, Concheiro Angel, Alvarez-Lorenzo Carmen
Instituto de Investigaciones en Ciencia y Tecnología de Materiales, INTEMA (UNMdP-CONICET), Av. Juan B. Justo 4302, B7608FDQ Mar del Plata, Argentina; Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+D Pharma Group (GI-1645), Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+D Pharma Group (GI-1645), Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Mater Sci Eng C Mater Biol Appl. 2017 Jun 1;75:1115-1127. doi: 10.1016/j.msec.2017.02.151. Epub 2017 Feb 28.
The replacement of small-diameter vessels is one of the main challenges in tissue engineering. Moreover, the surface modification of small-diameter vascular grafts (SDVG) is a key factor in the success of the therapy due to their increased thrombogenicity and infection susceptibility caused by the lack of a functional endothelium. In this work, electrospun scaffolds were prepared from blends of poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) with a composition designed to perform as SDVG inner layer. The scaffolds were then successfully surface-modified with heparin following two different strategies that rely on grafting of heparin to either PLLA or PHD functional groups. Both strategies afforded high heparin density, being higher for urethane methodology. The functionalized scaffolds did not cause hemolysis and inhibited platelet adhesion to a large extent. However, lysozyme/heparin-functionalized scaffolds obtained through urethane methodology achieved the highest platelet attachment inhibition. The increase in hydrophilicity and water absorption of the surface-functionalized nanostructures favored adhesion and proliferation of human adipose-derived stem cells. Heparinized surfaces conjugated with lysozyme presented microbial hydrolysis activity dependent on heparin content. Overall, a better performance obtained for urethane-modified scaffold, added to the fact that no chain scission is involved in urethane methodology, makes the latter the best choice for surface modification of PLLA/PHD 50/50 electrospun scaffolds. Scaffolds functionalized by this route may perform as advanced components of SDVG suitable for vascular tissue engineering, exhibiting biomimetic behavior, avoiding thrombi formation and providing antimicrobial features.
小直径血管的替代是组织工程中的主要挑战之一。此外，小直径血管移植物（SDVG）的表面改性是治疗成功的关键因素，因为缺乏功能性内皮会导致其血栓形成性增加和感染易感性增强。在这项工作中，由聚（L-乳酸）（PLLA）和分段聚氨酯（PHD）的共混物制备了电纺支架，其组成设计用作SDVG内层。然后，通过两种不同的策略成功地用肝素对支架进行了表面改性，这两种策略依赖于将肝素接枝到PLLA或PHD官能团上。两种策略都提供了高肝素密度，氨基甲酸酯方法的肝素密度更高。功能化支架不会引起溶血，并在很大程度上抑制血小板粘附。然而，通过氨基甲酸酯方法获得的溶菌酶/肝素功能化支架实现了最高的血小板附着抑制。表面功能化纳米结构的亲水性和吸水性增加有利于人脂肪来源干细胞的粘附和增殖。与溶菌酶共轭的肝素化表面呈现出依赖于肝素含量的微生物水解活性。总体而言，氨基甲酸酯改性支架表现出更好的性能，再加上氨基甲酸酯方法不涉及链断裂这一事实，使得后者成为PLLA/PHD 50/50电纺支架表面改性的最佳选择。通过这种途径功能化的支架可作为适合血管组织工程的SDVG的先进组件，表现出仿生行为，避免血栓形成并提供抗菌特性。
