Jana Soumen, Franchi Federico, Lerman Amir
Department of Bioengineering, University of Missouri, Columbia, MO 65211, USA.
Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Appl Mater Today. 2021 Sep;24. doi: 10.1016/j.apmt.2021.101112. Epub 2021 Jul 23.
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 on tissue 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 during tissue 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.
组织工程心脏瓣膜是人工心脏瓣膜一种很有前景的替代解决方案。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小叶三层定向结构的能力。在本研究中，我们利用静电纺丝技术开发了具有与天然小叶相似形态特征的三层微纤维小叶基质。将这些基质皮下植入大鼠体内，以研究其三层定向结构对组织工程的影响。组织构建体呈现出明确的结构，具有周向定向层、随机定向层和径向定向层。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，构建体的各向异性拉伸特性足以承受瓣膜生理负荷。最后，在驻留细胞中检测到波形蛋白和α-平滑肌肌动蛋白在基因和蛋白质水平的表达，揭示了它们的生长状态以及向肌成纤维细胞的转分化。我们的数据支持三层结构和各向异性特性在功能性小叶组织构建体中的关键作用，并表明小叶基质具有开发用于心脏瓣膜置换的瓣膜支架的潜力。
