Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Acta Biomater. 2019 Feb;85:142-156. doi: 10.1016/j.actbio.2018.12.005. Epub 2018 Dec 5.
Heart valve tissue engineering could be an alternative to the current bioprosthetic heart valve that faces limitations especially in pediatric patients. However, heart valve tissue engineering has remained challenging because leaflets - the primary component of a heart valve - have three layers with three diverse orientations - circumferential, random and radial, respectively. In order to mimic the orientations, we first designed three novel collectors to fabricate three nanofibrous layers with those orientations from a polymeric biomaterial in an electrospinning system. Then, we devised a novel direct electrospinning technique to develop a unified trilayered nanofibrous (TN) substrate comprising those oriented layers. The TN substrate supported the growth and orientations of seeded porcine valvular interstitial cells (PVICs) and their deposited collagen fibrils. After one month culture, the obtained trilayered tissue construct (TC) exhibited increased tensile properties over its TN substrate. Most importantly, the developed TC did not show any sign of shrinkage. Gene expression pattern of the PVICs indicated the developing stage of the TC. Their protein expression pattern was quite similar to that of leaflets. STATEMENT OF SIGNIFICANCE: This manuscript talks about development of a novel trilayered nanofibrous substrate mimicking the morphologies of a heart valve leaflet. It also describes culturing of valvular interstitial cells that reside in a leaflet, in the substrate and compares the behavior of the cultured cells with that in native leaflets in terms cell morphology, protein deposition and its orientation, and molecular signature. This study builds the groundwork for our future trilayered, tissue-engineered leaflet development. This research article would be of great interest to investigators and researchers in the field of cardiovascular tissue engineering especially in cardiac valve tissue engineering through biomaterial-based tissue engineering.
心脏瓣膜组织工程可能是目前生物瓣的替代方法，生物瓣尤其在儿科患者中面临局限性。然而，心脏瓣膜组织工程一直具有挑战性，因为瓣叶（心脏瓣膜的主要组成部分）具有三个分别具有圆周、随机和放射状取向的层。为了模拟这些取向，我们首先设计了三个新型收集器，以便在电纺系统中用聚合物生物材料制造具有这些取向的三个纳米纤维层。然后，我们设计了一种新颖的直接电纺技术，以开发一种包含这些取向层的统一的三层纳米纤维（TN）基底。TN 基底支持种子化的猪瓣膜间质细胞（PVIC）及其沉积的胶原纤维的生长和取向。经过一个月的培养，获得的三层组织构建体（TC）在其 TN 基底上表现出增加的拉伸性能。最重要的是，所开发的 TC 没有任何收缩的迹象。PVIC 的基因表达模式表明 TC 的发育阶段。它们的蛋白质表达模式与瓣叶非常相似。意义声明：本文讨论了一种新型三层纳米纤维基底的开发，该基底模仿心脏瓣膜瓣叶的形态。它还描述了在基底中培养位于瓣叶中的间质细胞，并根据细胞形态、蛋白质沉积及其取向和分子特征，将培养细胞的行为与天然瓣叶进行比较。这项研究为我们未来的三层、组织工程瓣叶的发展奠定了基础。这篇研究文章将引起心血管组织工程领域，特别是基于生物材料的心脏瓣膜组织工程领域的研究人员和研究人员的极大兴趣。
