Electrospun Polyurethane and Hydrogel Composite Scaffolds as Biomechanical Mimics for Aortic Valve Tissue Engineering.
Electrospun Polyurethane and Hydrogel Composite Scaffolds as Biomechanical Mimics for Aortic Valve Tissue Engineering.
复制标题
电纺聚氨酯和水凝胶复合支架作为主动脉瓣组织工程的生物力学模拟物。
DOI：
10.1021/acsbiomaterials.6b00309
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发表时间：
2016
影响因子：
5.8
通讯作者：
Grande-Allen,KJane
中科院分区：
文献类型：
--
作者：
Puperi,DanielS;Kishan,Alysha;Punske,ZoeE;Wu,Yan;Cosgriff-Hernandez,Elizabeth;West,JenniferL;Grande-Allen,KJane
在这项研究中，研究了由电纺聚氨酯和聚乙二醇水凝胶组成的复合支架用于主动脉瓣组织工程。这种多层方法可以制造满足所需机械要求的支架，同时实现细胞的 3D 培养。通过电纺聚氨酯网层的设计，对支架进行了调整，以模拟天然主动脉瓣的拉伸强度、各向异性和可延展性。瓣膜间质细胞被封装在静电纺丝网周围支架的水凝胶部分内，形成约 200 μm 厚的复合支架。电纺纤维的硬度导致封装的细胞表现出激活的表型，从而导致支架以异质方式发生纤维化重塑。通过在机械约束状态和弯曲状态下培养支架，进一步探索了重塑。受约束的支架表现出强烈的纤维化重塑，细胞沿机械约束的方向排列。弯曲支架证明施加的机械力可以影响细胞行为。接种在弯曲外曲线上的细胞表现出激活的纤维化反应，而接种在弯曲内曲线上的细胞呈现静止表型，这表明对细胞纤维化行为的潜在控制。总的来说，这些结果表明这种聚氨酯/水凝胶支架模仿了天然瓣膜的结构和功能异质性，值得进一步研究以用作了解纤维化瓣膜疾病的模型。
In this study, a composite scaffold consisting of an electrospun polyurethane and poly(ethylene glycol) hydrogel was investigated for aortic valve tissue engineering. This multilayered approach permitted the fabrication of a scaffold that met the desired mechanical requirements while enabling the 3D culture of cells. The scaffold was tuned to mimic the tensile strength, anisotropy, and extensibility of the natural aortic valve through design of the electrospun polyurethane mesh layer. Valve interstitial cells were encapsulated inside the hydrogel portion of the scaffold around the electrospun mesh, creating a composite scaffold approximately 200 μm thick. The stiffness of the electrospun fibers caused the encapsulated cells to exhibit an activated phenotype that resulted in fibrotic remodeling of the scaffold in a heterogeneous manner. Remodeling was further explored by culturing the scaffolds in both a mechanically constrained state and in a bent state. The constrained scaffolds demonstrated strong fibrotic remodeling with cells aligning in the direction of the mechanical constraint. Bent scaffolds demonstrated that applied mechanical forces could influence cell behavior. Cells seeded on the outside curve of the bend exhibited an activated, fibrotic response, while cells seeded on the inside curve of the bend were a quiescent phenotype, demonstrating potential control over the fibrotic behavior of cells. Overall, these results indicate that this polyurethane/hydrogel scaffold mimics the structural and functional heterogeneity of native valves and warrants further investigation to be used as a model for understanding fibrotic valve disease.