Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering.
Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering.
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DOI：
10.1002/adhm.201600699
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发表时间：
2016-12
影响因子：
10
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Campagnolo P;Gormley AJ;Chow LW;Guex AG;Parmar PA;Puetzer JL;Steele JA;Breant A;Madeddu P;Stevens MM
用于冠状动脉搭桥术的合成血管移植物的开发受到内皮化不足和缺乏天然细胞成分的挑战，内皮化不足暴露于血栓形成的风险，天然细胞成分有利于病理重塑。在这里，提出了一种具有合成血管移植物应用潜力的双功能电纺聚（ε-己内酯）（PCL）支架。该支架包含两个拴系的肽：骨桥蛋白衍生肽（Adh）的'管腔'侧和肝素结合肽（Hep）的'近腔'侧。此外，支架的“近腔”侧接种有隐静脉来源的周细胞（SVP）作为促血管生成生长因子的来源。Adh肽显著增加内皮细胞粘附，而Hep肽促进SVP分泌的血管内皮生长因子（VEGF）的积累。SVP增加了在PCL支架上进行的transwell试验和改良划痕试验中的内皮迁移。SVP接种在支架的“无腔”/Hep侧进一步增加内皮细胞密度，表明肽和周细胞的组合效应。最后，SVP接种的支架通过在无异种培养基中冷冻来保存，保持良好的细胞活力和功能。总之，这种工程支架结合了患者来源的周细胞和空间组织功能，协同增加内皮细胞密度和生长因子保留。
The development of synthetic vascular grafts for coronary artery bypass is challenged by insufficient endothelialization, which exposes to the risk of thrombosis, and lack of native cellular constituents, which favours pathological remodelling. Here, an bifunctional electrospun poly(ε-caprolactone) (PCL) scaffold with potential for synthetic vascular graft applications is presented. This scaffold incorporates two tethered peptides: the osteopontin-derived peptide (Adh) on the ‘luminal’ side and a heparin-binding peptide (Hep) on the ‘abluminal’ side. Additionally, the ‘abluminal’ side of the scaffold is seeded with saphenous vein-derived pericytes (SVPs) as a source of pro-angiogenic growth factors. The Adh peptide significantly increase endothelial cell adhesion, while the Hep peptide promote accumulation of vascular endothelial growth factor (VEGF) secreted by SVPs. SVPs increase endothelial migration both in a transwell assay and a modified scratch assay performed on the PCL scaffold. Seeding of SVPs on the ‘abluminal’/Hep side of the scaffold further increase endothelial cell density, indicating a combinatory effect of the peptides and pericytes. Lastly, SVP-seeded scaffolds are preserved by freezing in a xeno-free medium, maintaining good cell viability and function. In conclusion, this engineered scaffold combines patient-derived pericytes and spatially organized functionalities, which synergistically increase endothelial cell density and growth factor retention.