Department of Chemical and Biomolecular Engineering, University of California - Los Angeles, Los Angeles, CA 90095, USA.
Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA; Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Zapopan, JAL, Mexico.
Biomaterials. 2019 Jul;207:89-101. doi: 10.1016/j.biomaterials.2019.03.015. Epub 2019 Mar 21.
Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.
心肌梗死（MI）导致受损心脏部位的多相修复过程，最终导致非传导性纤维瘢痕组织的形成。尽管广泛使用导电生物材料来提高体外工程化心脏组织的生理相关性，但仍然存在一些与工程化具有适当机械性能和导电性的生物相容性支架相关的限制，以用于心脏组织再生。在这里，我们通过静电纺丝明胶甲基丙烯酰（GelMA）并随后缀合基于胆碱的生物离子液体（Bio-IL）来引入高度粘附的纤维支架，以开发导电和粘附性心脏贴片。优化这些 GelMA/Bio-IL 粘性贴片以使其具有类似于天然心肌的机械和导电性能。此外，由于 Bio-IL 与天然组织之间形成离子键，因此工程贴片强烈粘附于鼠类心肌，从而消除了缝合的需要。在 GelMA/Bio-IL 贴片上共培养的原代心肌细胞和心肌成纤维细胞表现出比原始 GelMA 对照更好的收缩曲线，这表现为间隙连接蛋白 connexin 43 的过表达。这些心脏贴片可用于提供机械支撑并恢复 MI 部位的机电耦联，以最小化心脏重构并保持正常心脏功能。
