Instituto de Investigaciones en Ciencia y Tecnología de Materiales, INTEMA (UNMdP-CONICET), Av. Cristóbal Colón 10850, B7606WV Mar del Plata, Argentina.
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Int J Biol Macromol. 2021 May 15;179:567-575. doi: 10.1016/j.ijbiomac.2021.03.008. Epub 2021 Mar 3.
One of the main challenges of cardiovascular tissue engineering is the development of bioresorbable and compliant small-diameter vascular grafts (SDVG) for patients where autologous grafts are not an option. In this work, electrospun bilayered bioresorbable SDVG based on blends of poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) were prepared and evaluated. The inner layer of these SDVG was surface-modified with heparin, following a methodology involving PHD urethane functional groups. Heparin was selected as anticoagulant agent, and also due to its ability to promote human umbilical vein endothelial cells (HUVECs) growth and to inhibit smooth muscle cells over-proliferation, main cause of neointimal hyperplasia and restenosis. Immobilized heparin was quantified and changes in SDVG microstructure were investigated through SEM. Tensile properties of the heparin-functionalized SDVG resembled those of saphenous vein. Vascular grafts were seeded with HUVECs and cultured on a flow-perfusion bioreactor to analyze the effect of heparin on graft endothelization under simulated physiological-like conditions. The analysis of endothelial cells attachment and gene expression (Real-Time PCR) pointed out that the surface functionalization with heparin successfully promoted a stable and functional endothelial cell layer.
心血管组织工程面临的主要挑战之一是为不能使用自体移植物的患者开发可生物吸收且顺应性好的小直径血管移植物 (SDVG)。在这项工作中，制备并评估了基于聚 L-乳酸 (PLLA) 和嵌段聚氨酯 (PHD) 共混物的电纺双层可生物吸收 SDVG。这些 SDVG 的内层用肝素进行表面改性，采用涉及 PHD 氨酯官能团的方法。肝素被选择为抗凝剂，也因为它能够促进人脐静脉内皮细胞 (HUVEC) 的生长并抑制平滑肌细胞过度增殖，这是导致新生内膜增生和再狭窄的主要原因。固定化肝素的量通过 SEM 进行了定量，并通过 SEM 研究了 SDVG 微观结构的变化。肝素功能化的 SDVG 的拉伸性能类似于大隐静脉。将 HUVEC 接种到血管移植物上，并在流灌注生物反应器中进行培养，以在模拟生理条件下分析肝素对移植物内皮化的影响。对内皮细胞附着和基因表达（实时 PCR）的分析表明，肝素的表面功能化成功促进了稳定且功能齐全的内皮细胞层。
