Fibrous heart valve leaflet substrate with native-mimicked morphology.
Fibrous heart valve leaflet substrate with native-mimicked morphology.
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具有模仿天然形态的纤维心脏瓣膜小叶基质。
DOI：
10.1016/j.apmt.2021.101112
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发表时间：
2021
影响因子：
8.3
通讯作者：
Lerman,Amir
中科院分区：
文献类型：
--
作者：
Jana,Soumen;Franchi,Federico;Lerman,Amir
组织工程心脏瓣膜是人工瓣膜的一种有前途的替代方案。然而，组织工程心脏瓣膜的长期功能取决于模仿天然心脏瓣膜瓣叶三层定向结构的能力。在这项研究中，使用静电纺丝，我们开发了三层微纤维瓣叶基板的形态特征类似于原生瓣叶。将其植入大鼠皮下，研究其三层定向结构在体内组织工程中的作用。组织构建体显示出明确的结构，具有周向取向层、随机取向层和径向取向层。在体内组织工程过程中产生的细胞外基质由胶原蛋白、糖胺聚糖和弹性蛋白组成，这些都是天然小叶的主要成分。此外，结构的各向异性拉伸性能足以承受瓣膜生理负荷。最后，在基因和蛋白水平上检测波形蛋白和α-平滑肌肌动蛋白在驻留细胞中的表达，揭示其生长状态和向肌成纤维细胞的转分化。我们的数据支持功能性瓣叶组织结构中的三层结构和各向异性特性的关键作用，并表明瓣叶基质具有开发用于心脏瓣膜置换的瓣膜支架的潜力。
Tissue-engineered heart valves are a promising alternative solution to prosthetic valves. However, long-term functionalities of tissue-engineered heart valves depend on the ability to mimic the trilayered, oriented structure of native heart valve leaflets. In this study, using electrospinning, we developed trilayered microfibrous leaflet substrates with morphological characteristics similar to native leaflets. The substrates were implanted subcutaneously in rats to study the effect of their trilayered oriented structure onin vivotissue engineering. The tissue constructs showed a well-defined structure, with a circumferentially oriented layer, a randomly oriented layer and a radially oriented layer. The extracellular matrix, produced duringin vivotissue engineering, consisted of collagen, glycosaminoglycans, and elastin, all major components of native leaflets. Moreover, the anisotropic tensile properties of the constructs were sufficient to bear the valvular physiological load. Finally, the expression of vimentin and α-smooth muscle actin, at the gene and protein level, was detected in the residing cells, revealing their growing state and their transdifferentiation to myofibroblasts. Our data support a critical role for the trilayered structure and anisotropic properties in functional leaflet tissue constructs, and indicate that the leaflet substrates have the potential for the development of valve scaffolds for heart valve replacements.