Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities

Abstract Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly...

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Main Authors: Mao Mao, Xiaoli Qu, Yabo Zhang, Bingsong Gu, Chen Li, Rongzhi Liu, Xiao Li, Hui Zhu, Jiankang He, Dichen Li
Format: Article
Language:English
Published: Nature Portfolio 2023-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-37716-1
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author Mao Mao
Xiaoli Qu
Yabo Zhang
Bingsong Gu
Chen Li
Rongzhi Liu
Xiao Li
Hui Zhu
Jiankang He
Dichen Li
author_facet Mao Mao
Xiaoli Qu
Yabo Zhang
Bingsong Gu
Chen Li
Rongzhi Liu
Xiao Li
Hui Zhu
Jiankang He
Dichen Li
author_sort Mao Mao
collection DOAJ
description Abstract Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.
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spelling doaj.art-9d66af2130864cfc91315ca15fa2494a2023-04-16T11:18:34ZengNature PortfolioNature Communications2041-17232023-04-0114111810.1038/s41467-023-37716-1Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalitiesMao Mao0Xiaoli Qu1Yabo Zhang2Bingsong Gu3Chen Li4Rongzhi Liu5Xiao Li6Hui Zhu7Jiankang He8Dichen Li9State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityState Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong UniversityAbstract Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.https://doi.org/10.1038/s41467-023-37716-1
spellingShingle Mao Mao
Xiaoli Qu
Yabo Zhang
Bingsong Gu
Chen Li
Rongzhi Liu
Xiao Li
Hui Zhu
Jiankang He
Dichen Li
Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
Nature Communications
title Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
title_full Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
title_fullStr Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
title_full_unstemmed Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
title_short Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
title_sort leaf venation directed cellular alignment for macroscale cardiac constructs with tissue like functionalities
url https://doi.org/10.1038/s41467-023-37716-1
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