Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, United States.
Integrated Nanosystems Development Institute and Department of Mechanical and Energy Engineering, Purdue School of Engineering and Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202, United States.
Acta Biomater. 2022 Feb;139:179-189. doi: 10.1016/j.actbio.2020.12.033. Epub 2020 Dec 19.
Tissue engineered cardiac patches have great potential as a therapeutic treatment for myocardial infarction (MI). However, for successful integration with the native tissue and proper function of the cells comprising the patch, it is crucial for these patches to mimic the ordered structure of the native extracellular matrix and the electroconductivity of the human heart. In this study, a new composite construct that can provide both conductive and topographical cues for human induced pluripotent stem cell derived cardiomyocytes (iCMs) is developed for cardiac tissue engineering applications. The constructs are fabricated by 3D printing conductive titanium carbide (TiCT) MXene in pre-designed patterns on polyethylene glycol (PEG) hydrogels, using aerosol jet printing, at a cell-level resolution and then seeded with iCMs and cultured for one week with no signs of cytotoxicity. The results presented in this work illustrate the vital role of 3D-printed TiCT MXene on aligning iCMs with a significant increase in MYH7, SERCA2, and TNNT2 expressions, and with an improved synchronous beating as well as conduction velocity. This study demonstrates that 3D printed TiCT MXene can potentially be used to create physiologically relevant cardiac patches for the treatment of MI. STATEMENT OF SIGNIFICANCE: As cardiovascular diseases and specifically myocardial infarction (MI) continue to be the leading cause of death worldwide, it is critical that new clinical interventions be developed. Tissue engineered cardiac patches have shown significant potential as clinical therapeutics to promote recovery following MI. Unfortunately, current constructs lack the ordered structure and electroconductivity of native human heart. In this study, we engineered a composite construct that can provide both conductive and topographical cues for human induced pluripotent stem cell derived cardiomyocytes. By 3D printing conductive TiCT MXene in pre-designed patterns on polyethylene glycol hydrogels, using aerosol jet printing, at a cell-level resolution, we developed tissue engineered patches that have the potential for providing a new clinical therapeutic to combat cardiovascular disease.
组织工程心脏贴片作为心肌梗死 (MI) 的治疗方法具有巨大的潜力。然而，为了使这些贴片与天然组织成功整合，并使构成贴片的细胞具有适当的功能，这些贴片必须模仿天然细胞外基质的有序结构和人类心脏的导电性。在这项研究中，开发了一种新的复合构建体，可为人类诱导多能干细胞衍生的心肌细胞 (iCMs) 提供导电和形貌线索，用于心脏组织工程应用。该构建体是通过气溶胶喷射印刷技术，以细胞级分辨率在聚乙二醇 (PEG) 水凝胶上 3D 打印预先设计图案的导电碳化钛 (TiCT) MXene 来制造的，然后接种 iCMs 并培养一周，无细胞毒性迹象。本工作中呈现的结果说明了 3D 打印 TiCT MXene 在对齐 iCMs 方面的重要作用，使 MYH7、SERCA2 和 TNNT2 的表达显著增加，同步跳动和传导速度也得到改善。这项研究表明，3D 打印 TiCT MXene 可用于为治疗 MI 创建具有生理相关性的心脏贴片。
由于心血管疾病，特别是心肌梗死 (MI) 仍然是全球范围内导致死亡的主要原因，因此必须开发新的临床干预措施。组织工程心脏贴片作为 MI 后促进恢复的临床治疗方法具有巨大的潜力。不幸的是，目前的构建体缺乏天然人类心脏的有序结构和导电性。在这项研究中，我们设计了一种复合构建体，可为人类诱导多能干细胞衍生的心肌细胞提供导电和形貌线索。通过气溶胶喷射印刷技术，以细胞级分辨率在聚乙二醇水凝胶上 3D 打印预先设计图案的导电 TiCT MXene，我们开发了具有提供新的临床治疗方法以对抗心血管疾病潜力的组织工程贴片。
