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Decellularized extracellular matrix bioinks and the external stimuli to enhance cardiac tissue development in vitro.

Authors
  • Das, Sanskrita1
  • Kim, Seok-Won2
  • Choi, Yeong-Jin3
  • Lee, Sooyeon1
  • Lee, Se-Hwan1
  • Kong, Jeong-Sik4
  • Park, Hun-Jun5
  • Cho, Dong-Woo6
  • Jang, Jinah7
  • 1 Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea. , (North Korea)
  • 2 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea. , (North Korea)
  • 3 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea; Department of Advanced Biomaterials Research, Materials Processing Innovation Research Division, Korea Institute of Materials Science (KIMS), 797 Changwon-daero, Seongsan-gu, Changwon-si, Gyeongsangnam-do, 51508, Republic of Korea. , (North Korea)
  • 4 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea. , (North Korea)
  • 5 Division of Cardiovascular Medicine, The Catholic University of Korea, College of Medicine, Cardiovascular Center, Seoul St. Mary's Hospital, 222 Banpodaero, Seocho-gu, Seoul 06591, Republic of Korea. , (North Korea)
  • 6 Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea. Electronic address: [email protected] , (North Korea)
  • 7 Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea; Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea. Electronic address: [email protected] , (North Korea)
Type
Published Article
Journal
Acta biomaterialia
Publication Date
Sep 01, 2019
Volume
95
Pages
188–200
Identifiers
DOI: 10.1016/j.actbio.2019.04.026
PMID: 30986526
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Engineered heart tissue (EHT) has ample potential as a model for in vitro tissue modeling or tissue regeneration. Using 3D cell printing technology, various hydrogels have been utilized as bioinks to fabricate EHT to date. However, its efficacy has remained limited due to poor functional properties of the cultured cardiomyocytes stemming from a lack of proper microenvironmental cues. Specifically, the surrounding matrix plays a key role in modulating cardiomyocyte differentiation and maturation. Recently, the use of heart tissue-derived extracellular matrix (hdECM) bioink has come to be seen as one of the most promising candidates due to its functional and structural similarities to native tissue. Here, we demonstrated a correlation between the synthesis of cardiomyocyte-specific proteins and the surrounding microenvironment irrespective of the similar material chemistry. Primary cardiomyocytes isolated from neonatal rats were encapsulated in different composition and concentration of bioinks (hdECM and collagen). The bioinks were sequentially printed using an extrusion-based 3D bioprinter and cultured either statically or dynamically. Qualitative and quantitative evaluation revealed enhanced maturation of cardiomyocytes in hdECM, unlike the collagen group under similar culture conditions. Specifically, 3D-printed EHT using a low concentration of hdECM promoted early differentiation of cardiomyocytes. Hence, the present study provides experimental insights regarding the establishment of a 3D-printed cardiac tissue model, highlighting that the matrix and the culture microenvironment can be decisive factors for cell-material interactions that affect cardiomyocyte maturation. STATEMENT OF SIGNIFICANCE: The regulation of signal transduction and responses to extracellular matrices (ECMs) is of particular relevance in tissue maturation. In particular, there is a clear need to understand the structural and phenotypical modulation in cardiomyocytes with respect to the surrounding microenvironment. Exploration of the key regulators, such as the compositional and the biophysical properties of bioinks associated directly with cell-cell and cell-matrix interactions would assist with the fabrication of cardiac tissue constructs with enhanced functionality. Hence, we documented the synergistic effects of surrounding matrices and culture conditions on the maturation of cardiomyocytes. Additionally, we highlighted the potential of using 3D bioprinting techniques to fabricate uniformly aligned cardiac constructs for mid- to high-throughput drug testing platforms that have great reproducibility and versatility. Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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