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Decellularized extracellular matrix bioinks and the external stimuli to enhance cardiac tissue development in vitro
- Source :
- Acta Biomaterialia. 95:188-200
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.
- Subjects :
- Cell Survival
Swine
0206 medical engineering
Cell
Biomedical Engineering
02 engineering and technology
Biochemistry
law.invention
Rats, Sprague-Dawley
Biomaterials
Extracellular matrix
law
Extracellular
medicine
Animals
Myocytes, Cardiac
RNA, Messenger
Molecular Biology
3D bioprinting
Decellularization
Tissue Engineering
Chemistry
Heart
General Medicine
021001 nanoscience & nanotechnology
020601 biomedical engineering
In vitro
Biomechanical Phenomena
Extracellular Matrix
Cell biology
Actin Cytoskeleton
Phenotype
medicine.anatomical_structure
Self-healing hydrogels
Calcium
Ink
Collagen
Signal transduction
Rheology
0210 nano-technology
Gels
Biotechnology
Subjects
Details
- ISSN :
- 17427061
- Volume :
- 95
- Database :
- OpenAIRE
- Journal :
- Acta Biomaterialia
- Accession number :
- edsair.doi.dedup.....f7a6440749012548d8e403ffc620af5d