School of Biomedical Engineering, Science and Health Systems, Department of Chemistry, Drexel University, Philadelphia, Pennsylvania, 19104, USA.
Biomacromolecules. 2011 Feb 14;12(2):399-408. doi: 10.1021/bm101149r. Epub 2010 Dec 23.
In search for novel biomimetic scaffolds for application in vascular tissue engineering, we evaluated a series of fibrous scaffolds prepared by coelectrospinning tertiary blends of poly(lactide-co-glycolide) (PLGA), gelatin, and elastin (PGE). By systematically varying the ratios of PLGA and gelatin, we could fine-tune fiber size and swelling upon hydration as well as the mechanical properties of the scaffolds. Of all PGE blends tested, PGE321 (PLGA, gelatin, elastin v/v/v ratios of 3:2:1) produced the smallest fiber size (317 ± 46 nm, 446 ± 69 nm once hydrated) and exhibited the highest Young's modulus (770 ± 131 kPa) and tensile strength (130 ± 7 kPa). All PGE scaffolds supported the attachment and metabolization of human endothelial cells (ECs) and bovine aortic smooth muscle cells (SMCs) with some variances in EC morphology and cytoskeletal spreading observed at 48 h postseeding, whereas no morphologic differences were observed at confluence (day 8). The rate of metabolization of ECs, but not of SMCs, was lower than that on tissue culture plastic and depended on the specific PGE composition. Importantly, PGE scaffolds were capable of guiding the organotypic distribution of ECs and SMCs on and within the scaffolds, respectively. Moreover, the EC monolayer generated on the PGE scaffold surface was nonthrombogenic and functional, as assessed by the basal and cytokine-inducible levels of mRNA expression and amidolytic activity of tissue factor, a key player in the extrinsic clotting cascade. Taken together, our data indicate the potential application of PGE scaffolds in vascular tissue engineering.
为了寻找可应用于血管组织工程的新型仿生支架，我们评估了一系列由聚（丙交酯-共-乙交酯）（PLGA）、明胶和弹性蛋白（PGE）三元共混物共纺丝制备的纤维支架。通过系统地改变 PLGA 和明胶的比例，我们可以微调纤维的大小和水合后的溶胀以及支架的机械性能。在所测试的所有 PGE 共混物中，PGE321（PLGA、明胶、弹性蛋白的体积比为 3:2:1）产生的纤维最小（317±46nm，水合后为 446±69nm），杨氏模量最高（770±131kPa），拉伸强度最高（130±7kPa）。所有 PGE 支架均支持人内皮细胞（EC）和牛主动脉平滑肌细胞（SMC）的附着和代谢，在接种后 48 小时观察到 EC 形态和细胞骨架扩散存在一些差异，而在汇合（第 8 天）时则没有观察到形态差异。EC 的代谢率（而不是 SMC 的代谢率）低于组织培养塑料，且取决于特定的 PGE 组成。重要的是，PGE 支架能够分别引导 EC 和 SMC 在支架上和支架内的器官样分布。此外，PGE 支架表面生成的 EC 单层是非血栓形成的和功能正常的，这可以通过组织因子的基础和细胞因子诱导的 mRNA 表达水平和蛋白水解活性来评估，组织因子是外源性凝血级联反应的关键因子。总之，我们的数据表明 PGE 支架在血管组织工程中的应用潜力。
