Department of Bioengineering, University of Washington, Seattle, WA, USA.
Department of Chemistry, Western Washington University, Bellingham, WA, USA.
J Mater Chem B. 2018 Nov 28;6(44):7185-7196. doi: 10.1039/C8TB01116H. Epub 2018 Jun 18.
We report on the development of bioinspired cardiac scaffolds made from electroconductive acid-modified silk fibroin-poly(pyrrole) (AMSF+PPy) substrates patterned with nanoscale ridges and grooves reminiscent of native myocardial extracellular matrix (ECM) topography to enhance the structural and functional properties of cultured human pluripotent stem cells (hPSC)-derived cardiomyocytes. Nanopattern fidelity was maintained throughout the fabrication and functionalization processes, and no loss in conductive behavior occurred due to the presence of the nanotopographical features. AMSF+PPy substrates were biocompatible and stable, maintaining high cell viability over a 21-day culture period while displaying no signs of PPy delamination. The presence of anisotropic topographical cues led to increased cellular organization and sarcomere development, and electroconductive cues promoted a significant improvement in the expression and polarization of connexin 43 (Cx43), a critical regulator of cell-cell electrical coupling. The combination of biomimetic topography and electroconductivity also increased the expression of genes that encode key proteins involved in regulating the contractile and electrophysiological function of mature human cardiac tissue.
我们报告了一种仿生心脏支架的开发，该支架由导电酸改性丝素蛋白-聚吡咯（AMSF+PPy）基底制成，基底表面具有纳米级的脊和槽，类似于天然心肌细胞外基质（ECM）的形貌，以增强培养的人多能干细胞（hPSC）衍生的心肌细胞的结构和功能特性。纳米图案保真度在整个制造和功能化过程中得以保持，并且由于存在纳米形貌特征，不会导致导电性能的丧失。AMSF+PPy 基底具有生物相容性和稳定性，在 21 天的培养期间保持高细胞活力，同时显示出 PPy 分层的迹象。各向异性形貌线索的存在导致细胞组织和肌节发育增加，而导电性线索促进了缝隙连接蛋白 43（Cx43）的表达和极化的显著改善，Cx43 是细胞间电耦联的关键调节剂。仿生形貌和导电性的结合还增加了编码调节成熟人心肌组织收缩和电生理功能的关键蛋白的基因的表达。
