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Development of an electrospun biomimetic polyurea scaffold suitable for vascular grafting

机译:适于血管移植的电纺仿生聚脲支架的研制

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摘要

The optimization of biomechanical and biochemical properties of a vascular graft to render properties relevant to physiological environments is a major challenge today. These critical properties of a vascular graft not only regulate its stability and integrity, but also control invasion of cells for scaffold remodeling permitting its integration with native tissue. In this work, we have synthesized a biomimetic scaffold by electrospinning a blend of a polyurea, poly(serinol hexamethylene urea) (PSHU), and, a polyester, poly-ε-caprolactone (PCL). Mechanical properties of the scaffold were varied by varying polymer blending ratio and electrospinning flow rate. Mechanical characterization revealed that scaffolds with lower PSHU content relative to PCL content resulted in elasticity close to native mammalian arteries. We also found that increasing electrospinning flow rates also increased the elasticity of the matrix. Optimization of elasticity generated scaffolds that enabled vascular smooth muscle cells (SMCs) to adhere, grow and maintain a SMC phenotype. The 30/70 scaffold also underwent slower degradation than scaffolds with higher PSHU content, thereby, providing the best option for in vivo remodeling. Further, Gly-Arg-Gly-Asp-Ser (RGD) covalently conjugated to the polyurea backbone in 30/70 scaffold resulted in significantly increased clotting times. Reducing surface thrombogenicity by the conjugation of RGD is critical to avoiding intimal hyperplasia. Hence, biomechanical and biochemical properties of a vascular graft can be balanced by optimizing synthesis parameters and constituent components. For these reasons, the optimized RGD-conjugated 30/70 scaffold electrospun at 2.5 or 5 mL/h has great potential as a suitable material for vascular grafting applications.
机译:如今,优化血管移植物的生物力学和生化特性以提供与生理环境相关的特性是一项重大挑战。血管移植物的这些关键特性不仅调节其稳定性和完整性,而且还控制细胞入侵以进行支架重塑,从而使其能够与天然组织整合。在这项工作中,我们通过静电纺丝聚脲,聚(丝氨醇六亚甲基脲)(PSHU)和聚酯,聚ε-己内酯(PCL)的混合物合成了仿生支架。支架的机械性能通过改变聚合物共混比和静电纺丝流速来改变。机械特征表明,相对于PCL含量,PSHU含量较低的支架产生的弹性接近哺乳动物的天然动脉。我们还发现,增加静电纺丝流速也会增加基质的弹性。弹性的优化产生了使血管平滑肌细胞(SMC)粘附,生长和维持SMC表型的支架。 30/70支架的降解也比具有较高PSHU含量的支架慢,因此,为体内重塑提供了最佳选择。此外,在30/70支架中共价结合至聚脲主链的Gly-Arg-Gly-Asp-Ser(RGD)导致凝血时间显着增加。通过RGD的缀合减少表面血栓形成对于避免内膜增生至关重要。因此,可以通过优化合成参数和组成成分来平衡血管移植物的生物力学和生化特性。由于这些原因,以2.5或5 mL / h进行电纺的优化的RGD共轭30/70支架电纺具有巨大的潜力,可作为适用于血管移植应用的材料。

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