Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts.
Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts.
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DOI：
10.1016/j.biomaterials.2013.08.082
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发表时间：
2013-12
期刊：
影响因子：
14
通讯作者：
Wang, Yadong
中科院分区：
文献类型：
--
作者：
Lee, Kee-Won;Johnson, Noah R.;Gao, Jin;Wang, Yadong
关键词：
宿主细胞募集对于血管移植物重建和与天然血管的整合至关重要，对于依赖宿主重建的无细胞策略尤为重要。血管移植物生长因子的受控释放可能会增强宿主细胞的募集。基质细胞衍生因子-1α可诱导宿主祖细胞迁移和募集，但由于其体内半衰期较短，其在再生治疗中的潜力往往受到限制。本报告描述了一种凝聚给药系统，用于通过给予sdf-1α的保护来增强祖细胞在弹性血管移植物中的募集。肝素和合成的聚阳离子被用来形成凝聚体，它被结合到聚(庚二酸甘油)(PGS)支架中。除了保护sdf-1α外，凝聚体还有助于均匀的支架涂层。凝聚负载支架具有很高的SDF-1α负载效率，并在静态和生理相关的流动条件下提供持续释放，初始突发释放最少。体外实验表明，聚集态支架通过保持稳定的SDF-1α梯度，促进人内皮祖细胞和间充质祖细胞的迁移和渗透。这些结果表明，SDF-1α聚集态支架在原位血管再生中具有良好的应用前景。
Host cell recruitment is crucial for vascular graft remodeling and integration into the native blood vessel; it is especially important for cell-free strategies which rely on host remodeling. Controlled release of growth factors from vascular grafts may enhance host cell recruitment. Stromal cell-derived factor (SDF)-1α has been shown to induce host progenitor cell migration and recruitment; however, its potential in regenerative therapies is often limited due to its short half-life in vivo. This report describes a coacervate drug delivery system for enhancing progenitor cell recruitment into an elastomeric vascular graft by conferring protection of SDF-1α. Heparin and a synthetic polycation are used to form a coacervate, which is incorporated into poly(glycerol sebacate) (PGS) scaffolds. In addition to protecting SDF-1α, the coacervate facilitates uniform scaffold coating. Coacervate-laden scaffolds have high SDF-1α loading efficiency and provide sustained release under static and physiologically-relevant flow conditions with minimal initial burst release. In vitro assays showed that coacervate-laden scaffolds enhance migration and infiltration of human endothelial and mesenchymal progenitor cells by maintaining a stable SDF-1α gradient. These results suggest that SDF-1α coacervate-laden scaffolds show great promise for in situ vascular regeneration.
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