Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Republic of Korea.
Biofabrication. 2021 Aug 31;13(4). doi: 10.1088/1758-5090/ac1e78.
A novel tissue engineering strategy using 3D bio-print technology has become a promising therapeutic method for acute myocardial infarction (AMI) in an animal model. However, the application of 3D bio-printed tissue remains limited due to poor graft survival. Therefore, it is a scientific priority to enhance graft survival by precisely adjusting the 3D environment of encapsulated cells. In this study, novel transplantable 3D cardiac mesh (cMesh) tissue with a porous mesh structure was presented using human cardiomyocytes, human cardiac fibroblasts, and gelatin-methacryloyl-collagen hydrogel. Cardiomyocytes and cardiac fibroblasts were well spreaded. The cardiomyocytes were connected with a gap junction channel in bio-printed cMesh and a 3D cardiac patch with an aggregated structure. Porous cMesh demonstrated structural advantages by increased phosphorylation of mTOR, AKT, and ERK signals associated with cell survival. Transplanted cMesh in rats with AMI improved long-term graft survival, vessel formation, and stabilization, reduced fibrosis, increased left ventricle thickness, and enhanced cardiac function. Our results suggest that porous cMesh provides structural advantages and a positive therapeutic effect in an AMI animal model.
一种使用 3D 生物打印技术的新型组织工程策略已成为动物模型中急性心肌梗死（AMI）的一种有前途的治疗方法。然而，由于移植物存活率低，3D 生物打印组织的应用仍然受到限制。因此，通过精确调整细胞包封的 3D 环境来提高移植物存活率是一个科学优先事项。在这项研究中，使用人心肌细胞、人心肌成纤维细胞和明胶甲基丙烯酰胶原水凝胶构建了具有多孔网格结构的新型可移植 3D 心脏网格（cMesh）组织。心肌细胞和心肌成纤维细胞在生物打印的 cMesh 中得到了很好的扩展，形成了具有聚集结构的 3D 心脏贴片。多孔 cMesh 通过增加与细胞存活相关的 mTOR、AKT 和 ERK 信号的磷酸化显示出结构优势。在 AMI 大鼠中移植 cMesh 可提高移植物的长期存活率、血管形成和稳定性，减少纤维化，增加左心室厚度并增强心脏功能。我们的结果表明，多孔 cMesh 在 AMI 动物模型中提供了结构优势和积极的治疗效果。
