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Dual antibody functionalized polyvinyl alcohol and alginate hydrogels for synergistic endothelial cell adhesion.

机译:双抗体功能化的聚乙烯醇和藻酸盐水凝胶,用于协同内皮细胞粘附。

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摘要

Motivated by the need to design minimally-invasive treatments for wide-necked cerebral aneurysms, we used computational modeling to assess aneurysm hemodynamics, examined in vitro cellular responses arising from mechanical and chemical stresses, and designed novel materials that cooperatively adhere to the endothelium. We first hypothesized that because aneurysm geometry plays an important role in hemodynamics, changes in flow patterns may affect the shear stress experienced on the aneurysm wall. We defined flow regimes based on aneurysm hemodynamic and geometric parameters, which may correlate with aneurysm rupture. Because of the direct contact between endothelial cells (ECs) and blood flow, we then evaluated how changes in hemodynamics and inflammatory cytokines affect the expression of cell adhesion molecules (CAMs) and matrix remodeling factors on ECs. We subsequently designed biomaterials that complement the dynamic EC surface and have the ability to conform to any geometry through in situ crosslinking. Antibody-conjugated hydrogels facilitated synergistic EC adhesion using cooperativity as an adhesion strategy. We optimized the presentation of antibodies to inflammatory CAMs on polyvinyl alcohol (PVA) and alginate hydrogels to achieve strong adhesion to inflamed ECs. We synthesized photocrosslinkable, aminated PVA hydrogels and determined the effect of substrate stiffness on cell adhesion. We also evaluated the effects of antibody presentation on cell adhesion strength and dynamics using alginate hydrogels. Taken together, the results of this work may be used to design hydrogels for vascular remodeling applications under shear stress, including embolic agents for cerebral aneurysms.
机译:出于对颈宽动脉瘤设计微创治疗方法的需求,我们使用计算模型来评估动脉瘤的血流动力学,检查了机械和化学应力引起的体外细胞反应,并设计了可协同粘附于内皮的新型材料。我们首先假设,由于动脉瘤的几何形状在血液动力学中起着重要的作用,因此流动模式的变化可能会影响动脉瘤壁上的剪切应力。我们根据动脉瘤的血流动力学和几何参数定义了血流状况,这可能与动脉瘤破裂有关。由于内皮细胞(EC)和血流之间的直接接触,因此我们评估了血流动力学和炎性细胞因子的变化如何影响EC上细胞粘附分子(CAM)和基质重塑因子的表达。随后,我们设计了生物材料,这些材料可补充动态EC表面,并具有通过原位交联而符合任何几何形状的能力。抗体缀合的水凝胶使用协同作用作为粘附策略,促进了协同EC粘附。我们优化了聚乙烯醇(PVA)和藻酸盐水凝胶上抗炎性CAM抗体的呈递,以实现与发炎EC的牢固粘附。我们合成了可光交联的胺化PVA水凝胶,并确定了底物刚度对细胞粘附的影响。我们还使用藻酸盐水凝胶评估了抗体呈递对细胞粘附强度和动力学的影响。两者合计,这项工作的结果可用于设计在剪切应力下用于血管重塑应用的水凝胶,包括用于脑动脉瘤的栓塞剂。

著录项

  • 作者

    Rafat, Marjan.;

  • 作者单位

    Harvard University.;

  • 授予单位 Harvard University.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 154 p.
  • 总页数 154
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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