School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China.
Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
Mater Sci Eng C Mater Biol Appl. 2018 Apr 1;85:37-46. doi: 10.1016/j.msec.2017.12.005. Epub 2017 Dec 15.
Surface modification for rapid endothelialization of vascular biomaterials is known as an important way to prevent thrombosis and intimal hyperplasia. Moreover, therapeutical manipulation of microRNAs (miRNAs) expression via local delivery of miRNA mimics or inhibitors by electrospun ultrafine fibers has demonstrated the promise in tissue regeneration. In this work, a dual-functional electrospun membrane was developed by combining Arg-Glu-Asp-Val (REDV) peptide-modification of the fiber surface to enhance vascular endothelial cell (VEC) adhesion and encapsulation of miRNA-126 (miR-126) complexes in the electrospun fibers to accelerate VEC proliferation. The electrospun membranes were specially prepared by emulsion electrospinning of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) and REDV-terminated polycaprolactone (PCL) (50/50 mass ratio), in which miR-126 was encapsulated via REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol). By introduction of REDV-terminated PCL with lower molecular weight, the obtained electrospun fibers could be modified by REDV on their surface, and also achieve a relatively fast release profile of miR-126 in favor of VEC proliferation. Results of direct seeding VECs on the electrospun membranes indicated the enhanced cell adhesion and proliferation. The combination of REDV peptide-modification of the electrospun fibrous membranes and controllable miRNA release may provide a synergistic strategy of surface guidance and biochemical signals to support and modulate VECs for vascular tissue regeneration.
表面修饰可促进血管生物材料的快速内皮化,这被认为是预防血栓和内膜增生的重要方法。此外,通过电纺超细纤维局部递送电针对 miRNA(miRNA)表达的治疗性操作已证明在组织再生方面具有潜力。在这项工作中,通过将纤维表面的 Arg-Glu-Asp-Val(REDV)肽修饰与电纺纤维中 miRNA-126(miR-126)复合物的封装相结合,开发了一种具有双重功能的电纺膜,以增强血管内皮细胞(VEC)的黏附和增殖。通过聚乙二醇-b-聚(L-丙交酯-co-ε-己内酯)(PELCL)和 REDV 末端聚己内酯(PCL)(质量比为 50/50)的乳液静电纺丝专门制备了电纺膜,其中 miR-126 通过 REDV 肽修饰的三甲基壳聚糖-g-聚乙二醇封装。通过引入低分子量的 REDV 末端 PCL,可对所得电纺纤维的表面进行 REDV 修饰,并实现 miR-126 的相对较快释放,有利于 VEC 的增殖。将 VEC 直接接种到电纺膜上的结果表明,细胞黏附和增殖能力得到了增强。电纺纤维膜的 REDV 肽修饰与可控 miRNA 释放的结合可能为支持和调节 VEC 用于血管组织再生提供一种表面引导和生化信号协同的策略。