Wu Yong, Wang Yaning, Xiao Miao, Zhang Guangming, Zhang Feixiang, Tang Mingliang, Lei Wei, Jiang Ziyun, Li Xiaoyun, Zhang Huiqi, Ren Xiaoyi, Xu Yue, Zhao Xiaotong, Guo Chenxu, Lan Hongbo, Shen Zhenya, Zhang Jianyi, Hu Shijun
Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, China.
Shandong Engineering Research Center for Additive Manufacturing, Qingdao University of Technology, Qingdao, Shandong, 266520, China.
Adv Sci (Weinh). 2025 Mar;12(10):e2409871. doi: 10.1002/advs.202409871. Epub 2025 Jan 22.
Despite advancements in engineered heart tissue (EHT), challenges persist in achieving accurate dimensional accuracy of scaffolds and maturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), a primary source of functional cardiac cells. Drawing inspiration from cardiac muscle fiber arrangement, a three-dimensional (3D)-printed multi-layered microporous polycaprolactone (PCL) scaffold is created with interlayer angles set at 45° to replicate the precise structure of native cardiac tissue. Compared with the control group and 90° PCL scaffolds, the 45° PCL scaffolds exhibited superior biocompatibility for cell culture and improved hiPSC-CM maturation in calcium handling. RNA sequencing demonstrated that the 45° PCL scaffold promotes the mature phenotype in hiPSC-CMs by upregulating ion channel genes. Using the 45° PCL scaffold, a multi-cellular EHT is successfully constructed, incorporating human cardiomyocytes, endothelial cells, and mesenchymal stem cells. These complex EHTs significantly enhanced hiPSC-CM engraftment in vivo, attenuated ventricular remodeling, and improved cardiac function in mouse myocardial infarction. In summary, the myocardium-specific structured EHT developed in this study represents a promising advancement in cardiovascular regenerative medicine.
尽管工程心脏组织（EHT）取得了进展，但在实现支架的精确尺寸精度以及使人类诱导多能干细胞衍生的心肌细胞（hiPSC-CM）成熟方面仍存在挑战，hiPSC-CM是功能性心脏细胞的主要来源。从心肌纤维排列中汲取灵感，创建了一种三维（3D）打印的多层微孔聚己内酯（PCL）支架，其层间角度设置为45°，以复制天然心脏组织的精确结构。与对照组和90°PCL支架相比，45°PCL支架在细胞培养方面表现出卓越的生物相容性，并在钙处理方面改善了hiPSC-CM的成熟度。RNA测序表明，45°PCL支架通过上调离子通道基因促进hiPSC-CM中的成熟表型。使用45°PCL支架，成功构建了一种多细胞EHT，其中包含人类心肌细胞、内皮细胞和间充质干细胞。这些复杂的EHT显著增强了hiPSC-CM在体内的植入，减轻了心室重构，并改善了小鼠心肌梗死模型中的心脏功能。总之，本研究中开发的心肌特异性结构化EHT代表了心血管再生医学领域一项有前景的进展。
