Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels.
Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels.
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DOI：
10.1016/j.actbio.2010.08.018
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发表时间：
2011-01
影响因子：
9.7
通讯作者：
West, Jennifer L.
中科院分区：
文献类型：
--
作者：
Saik, Jennifer E.;Gould, Daniel J.;Watkins, Emily M.;Dickinson, Mary E.;West, Jennifer L.
组织工程领域由于组织工程构建物中缺乏微血管化而受到严重限制。仿生聚（乙二醇）水凝胶含有共价固定血小板衍生生长因子BB（PDGF-BB）的开发，以促进血管生成。聚（乙二醇）水凝胶抵抗蛋白质吸收和随后的非特异性细胞粘附，从而提供了一个“空白状态”，可以通过掺入细胞粘附配体和生长因子进行修饰。PDGF-BB是一种关键的血管生成蛋白，能够通过诱导功能性坏死和募集周细胞来支持新血管稳定。由于PDGF在体内的广泛作用和在循环血液中仅30分钟的半衰期，PDGF-BB的固定可能是必要的。在这项工作中，具有生物活性的、共价固定的PDGF-BB被证明可以诱导二维改性表面上的小管形成、三维（3D）可降解水凝胶中的迁移以及小鼠角膜微袋血管生成试验中的血管生成。共价固定的PDGF-BB还与共价固定的成纤维细胞生长因子-2组合使用，与单独呈现每种因子相比，这导致3D可降解水凝胶中内皮细胞迁移显著增加。当共培养的内皮细胞和小鼠周细胞前体10 T1/2细胞接种到改性表面上的小管形成是独立的表面修饰与共价固定的生长因子。此外，当植入体内小鼠角膜微袋血管生成测定中时，与单独的可溶性PDGF-BB相比，可溶性PDGF-BB和固定化PDGF-BB的组合诱导了更稳健的血管反应。基于这些结果，我们相信生物活性水凝胶可以定制，以改善组织工程的功能性微血管的形成。
The field of tissue engineering is severely limited by a lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent non-specific cell adhesion, thus providing a “blank slate”, which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to the widespread effects of PDGF in the body and a half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on two-dimensional modified surfaces, migration in three-dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea micro-pocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized fibroblast growth factor-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels compared with the presentation of each factor alone. When a co-culture of endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared with soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering.
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