Department of Bioengineering, University of Missouri, Columbia, Missouri 65211, United States.
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, United States.
ACS Appl Bio Mater. 2021 Nov 15;4(11):7836-7847. doi: 10.1021/acsabm.1c00768. Epub 2021 Nov 3.
Mechanical and bioprosthetic valves that are currently applied for replacing diseased heart valves are not fully efficient. Heart valve tissue engineering may solve the issues faced by the prosthetic valves in heart valve replacement. The leaflets of native heart valves have a trilayered structure with layer-specific orientations; thus, it is imperative to develop functional leaflet tissue constructs with a native trilayered, oriented structure. Its key solution is to develop leaflet scaffolds with a native morphology and structure. In this study, microfibrous leaflet scaffolds with a native trilayered and oriented structure were developed in an electrospinning system. The scaffolds were implanted for 3 months in rats subcutaneously to study the scaffold efficiencies in generating functional tissue-engineered leaflet constructs. These in vivo tissue-engineered leaflet constructs had a trilayered, oriented structure similar to native leaflets. The tensile properties of constructs indicated that they were able to endure the hydrodynamic load of the native heart valve. Collagen, glycosaminoglycans, and elastin─the predominant extracellular matrix components of native leaflets─were found sufficiently in the leaflet tissue constructs. The residing cells in the leaflet tissue constructs showed vimentin and α-smooth muscle actin expression, i.e., the constructs were in a growing state. Thus, the trilayered, oriented fibrous leaflet scaffolds produced in this study could be useful to develop heart valve scaffolds for successful heart valve replacements.
目前用于替换病变心脏瓣膜的机械瓣膜和生物瓣膜并非完全有效。心脏瓣膜组织工程可能解决心脏瓣膜置换中人工瓣膜面临的问题。天然心脏瓣膜的瓣叶具有三层结构，具有特定的层取向；因此，开发具有天然三层、定向结构的功能性瓣叶组织构建体至关重要。其关键解决方案是开发具有天然形态和结构的瓣叶支架。在这项研究中，在静电纺丝系统中开发了具有天然三层和定向结构的微纤维瓣叶支架。将支架植入大鼠皮下 3 个月，以研究支架在生成功能性组织工程瓣叶构建体方面的效率。这些体内组织工程瓣叶构建体具有类似于天然瓣叶的三层、定向结构。构建体的拉伸性能表明它们能够承受天然心脏瓣膜的流体动力负荷。在瓣叶组织构建体中发现了大量的胶原蛋白、糖胺聚糖和弹性蛋白——天然瓣叶的主要细胞外基质成分。瓣叶组织构建体中的驻留细胞表达波形蛋白和α-平滑肌肌动蛋白，即构建体处于生长状态。因此，本研究中制备的具有三层、定向纤维的瓣叶支架可用于开发成功的心脏瓣膜置换用心脏瓣膜支架。
