Micropatterning of Poly(Ethylene Glycol) Diacrylate Hydrogels with Biomolecules to Regulate and Guide Endothelial Morphogenesis
Micropatterning of Poly(Ethylene Glycol) Diacrylate Hydrogels with Biomolecules to Regulate and Guide Endothelial Morphogenesis
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DOI：
10.1089/ten.tea.2008.0196
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发表时间：
2009-03-01
影响因子：
4.1
通讯作者：
West, Jennifer L.
中科院分区：
文献类型：
--
作者：
Moon, James J.;Hahn, Mariah S.;West, Jennifer L.
血管生成是在新血管形成过程中由内皮细胞（EC）进行的形态发生，传统上研究天然细胞外基质蛋白。在这项工作中，我们的目的是调节和引导血管生成的合成，生物活性的聚（乙二醇）-二丙烯酸酯（PEGDA）水凝胶。PEGDA水凝胶本质上是细胞非粘附性的，并且对蛋白质吸附具有高度抗性，允许高度控制用于细胞粘附和信号传导的配体的呈递。由于这些材料是可光聚合的，因此可以应用各种微生物技术来空间控制生物活性配体的呈现。为了操纵EC粘附、迁移和小管形成，PEGDA水凝胶的表面用细胞粘附配体Arg-Gly-Asp-Ser（RGDS）以期望的浓度和几何形状进行微图案化。这些RGDS模式上培养的EC重组他们的细胞体成索状结构上的50毫米宽的条纹，但不是更宽的条纹，这表明EC形态可以调节几何线索。内皮细胞形成的索状结构使人联想到毛细血管，细胞参与自组装和重组成多细胞结构。此外，中等浓度的RGDS（20 μ g/cm 2）刺激内皮索形成，而高浓度则抑制内皮索形成。这项工作表明，血管生成反应可以通过生物活性配体的微图案化来严格调节和引导，并且还证明了微图案化PEGDA水凝胶在组织工程中的各种应用的巨大潜力，其中植入前的血管化是至关重要的。
Angiogenesis, which is morphogenesis undertaken by endothelial cells (ECs) during new blood vessel formation, has been traditionally studied on natural extracellular matrix proteins. In this work, we aimed to regulate and guide angiogenesis on synthetic, bioactive poly(ethylene glycol)-diacrylate (PEGDA) hydrogels. PEGDA hydrogel is intrinsically cell nonadhesive and highly resistant to protein adsorption, allowing a high degree of control over presentation of ligands for cell adhesion and signaling. Since these materials are photopolymerizable, a variety of photolithographic technologies may be applied to spatially control presentation of bioactive ligands. To manipulate EC adhesion, migration, and tubulogenesis, the surface of PEGDA hydrogels was micropatterned with a cell adhesive ligand, Arg-Gly-Asp-Ser (RGDS), in desired concentrations and geometries. ECs cultured on these RGDS patterns reorganized their cell bodies into cord-like structures on 50-mm-wide stripes, but not on wider stripes, suggesting that EC morphogenesis can be regulated by geometrical cues. The cords formed by ECs were reminiscent of capillaries with cells participating in the self-assembly and reorganization into multicellular structures. Further, endothelial cord formation was stimulated on intermediate concentration of RGDS at 20 mu g/cm(2), whereas it was inhibited at higher concentrations. This work has shown that angiogenic responses can be tightly regulated and guided by micropatterning of bioactive ligands and also demonstrated great potentials of micropatterned PEGDA hydrogels for various applications in tissue engineering, where vascularization prior to implantation is critical.