3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction
Abstract 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 cardi...
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409871 |
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| author | Yong Wu Yaning Wang Miao Xiao Guangming Zhang Feixiang Zhang Mingliang Tang Wei Lei Ziyun Jiang Xiaoyun Li Huiqi Zhang Xiaoyi Ren Yue Xu Xiaotong Zhao Chenxu Guo Hongbo Lan Zhenya Shen Jianyi Zhang Shijun Hu |
| author_facet | Yong Wu Yaning Wang Miao Xiao Guangming Zhang Feixiang Zhang Mingliang Tang Wei Lei Ziyun Jiang Xiaoyun Li Huiqi Zhang Xiaoyi Ren Yue Xu Xiaotong Zhao Chenxu Guo Hongbo Lan Zhenya Shen Jianyi Zhang Shijun Hu |
| author_sort | Yong Wu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-e051e99eb66647238c989e430adcbd05 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e051e99eb66647238c989e430adcbd052025-08-20T03:10:53ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.2024098713D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial InfarctionYong Wu0Yaning Wang1Miao Xiao2Guangming Zhang3Feixiang Zhang4Mingliang Tang5Wei Lei6Ziyun Jiang7Xiaoyun Li8Huiqi Zhang9Xiaoyi Ren10Yue Xu11Xiaotong Zhao12Chenxu Guo13Hongbo Lan14Zhenya Shen15Jianyi Zhang16Shijun Hu17Institute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaShandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology Qingdao Shandong 266520 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaInstitute 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 ChinaShandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology Qingdao Shandong 266520 ChinaShandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology Qingdao Shandong 266520 ChinaInstitute 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 ChinaDepartment of Biomedical Engineering School of Medicine and School of Engineering The University of Alabama at Birmingham Birmingham AL 35233 USAInstitute 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 ChinaAbstract 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.https://doi.org/10.1002/advs.2024098713D printingengineered heart tissuemyocardial infarctionmyocardium‐specific structure |
| spellingShingle | Yong Wu Yaning Wang Miao Xiao Guangming Zhang Feixiang Zhang Mingliang Tang Wei Lei Ziyun Jiang Xiaoyun Li Huiqi Zhang Xiaoyi Ren Yue Xu Xiaotong Zhao Chenxu Guo Hongbo Lan Zhenya Shen Jianyi Zhang Shijun Hu 3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction Advanced Science 3D printing engineered heart tissue myocardial infarction myocardium‐specific structure |
| title | 3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction |
| title_full | 3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction |
| title_fullStr | 3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction |
| title_full_unstemmed | 3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction |
| title_short | 3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction |
| title_sort | 3d printed myocardium specific structure enhances maturation and therapeutic efficacy of engineered heart tissue in myocardial infarction |
| topic | 3D printing engineered heart tissue myocardial infarction myocardium‐specific structure |
| url | https://doi.org/10.1002/advs.202409871 |
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