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  • Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation.

Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation.

Progress in biomaterials (2020-09-27)
Matthew Alonzo, Shweta Anil Kumar, Shane Allen, Monica Delgado, Fabian Alvarez-Primo, Laura Suggs, Binata Joddar
ABSTRACT

Hydrogels are a class of biomaterials used for a wide range of biomedical applications, including as a three-dimensional (3D) scaffold for cell culture that mimics the extracellular matrix (ECM) of native tissues. To understand the role of the ECM in the modulation of cardiac cell function, alginate was used to fabricate crosslinked gels with stiffness values that resembled embryonic (2.66 ± 0.84 kPa), physiologic (8.98 ± 1.29 kPa) and fibrotic (18.27 ± 3.17 kPa) cardiac tissues. The average pore diameter and hydrogel swelling were seen to decrease with increasing substrate stiffness. Cardiomyocytes cultured within soft embryonic gels demonstrated enhanced cell spreading, elongation, and network formation, while a progressive increase in gel stiffness diminished these behaviors. Cell viability decreased with increasing hydrogel stiffness. Furthermore, cells in fibrotic gels showed enhanced protein expression of the characteristic cardiac stress biomarker, Troponin-I, while reduced protein expression of the cardiac gap junction protein, Connexin-43, in comparison to cells within embryonic gels. The results from this study demonstrate the role that 3D substrate stiffness has on cardiac tissue formation and its implications in the development of complex matrix remodeling-based conditions, such as myocardial fibrosis.

MATERIALS
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Sigma-Aldrich
AC16 Human Cardiomyocyte Cell Line, AC16 Human Cardiomyocytes can be serially passaged and can differentiate when cultured in mitogen-free medium. The cells may be used to study developmental regulation of cardiomyocytes.