Hyaluronan Hydrogels for a Biomimetic Spongiosa Layer of Tissue Engineered Heart Valve Scaffolds.
Hyaluronan Hydrogels for a Biomimetic Spongiosa Layer of Tissue Engineered Heart Valve Scaffolds.
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DOI：
10.1021/acs.biomac.6b00180
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发表时间：
2016-05-09
影响因子：
6.2
通讯作者：
Grande-Allen KJ
中科院分区：
文献类型：
--
作者：
Puperi DS;O'Connell RW;Punske ZE;Wu Y;West JL;Grande-Allen KJ
先进的组织工程心脏瓣膜必须由多种材料构建，以更好地模拟天然瓣膜的异质性。主动脉瓣的三层结构提供了在人的一生中持续打开和关闭的能力，每一层都有特定的机械功能。中间海绵层主要由蛋白聚糖和糖胺聚糖组成，在阀门小叶弯曲打开和关闭时起润滑和阻尼作用。在这项研究中，透明质酸水凝胶被调整为执行海绵层的机械功能，为组织工程应用提供了一种仿生支架，其中瓣膜细胞被封装在3D中，并深入了解瓣膜细胞如何维持心脏瓣膜内的透明质酸稳态。透明质酸合酶HAS1异构体在透明质酸水凝胶中的表达明显高于空白板岩聚乙二醇二丙烯酸酯（PEGDA）水凝胶。透明质酸酶和基质金属蛋白酶活性在透明质酸和PEGDA水凝胶之间是相似的，尽管这些支架材料都特别容易被不同类型的酶降解。KIAA1199在瓣膜细胞中表达，可能参与心脏瓣膜透明质酸的调节。交联透明质酸水凝胶在3D培养中保持瓣膜细胞的健康表型，并被调整为接近瓣膜海绵层的机械特性。因此，透明质酸可以作为一种合适的材料用于拟议的层状组织工程心脏瓣膜支架的海绵状层。
Advanced tissue engineered heart valves must be constructed from multiple materials to better mimic the heterogeneity found in the native valve. The trilayered structure of aortic valves provides the ability to open and close consistently over a full human lifetime, with each layer performing specific mechanical functions. The middle spongiosa layer consists primarily of proteoglycans and glycosaminoglycans, providing lubrication and dampening functions as the valve leaflet flexes open and closed. In this study, hyaluronan hydrogels were tuned to perform the mechanical functions of the spongiosa layer, provide a biomimetic scaffold in which valve cells were encapsulated in 3D for tissue engineering applications, and gain insight into how valve cells maintain hyaluronan homeostasis within heart valves. Expression of the HAS1 isoform of hyaluronan synthase was significantly higher in hyaluronan hydrogels compared to blank-slate poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Hyaluronidase and matrix metalloproteinase enzyme activity was similar between hyaluronan and PEGDA hydrogels, even though these scaffold materials were each specifically susceptible to degradation by different enzyme types. KIAA1199 was expressed by valve cells and may play a role in the regulation of hyaluronan in heart valves. Cross-linked hyaluronan hydrogels maintained healthy phenotype of valve cells in 3D culture and were tuned to approximate the mechanical properties of the valve spongiosa layer. Therefore, hyaluronan can be used as an appropriate material for the spongiosa layer of a proposed laminate tissue engineered heart valve scaffold.