Open AccessHydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation
Author(s) -
Matthew Alonzo,
Shweta Kumar,
Shane C. Allen,
Mònica Delgado,
Fabian Alvarez-Primo,
Laura J. Suggs,
Binata Joddar
Publication year - 2020
Publication title -
progress in biomaterials
Language(s) - English
Resource type - Journals
eISSN - 2194-0509
pISSN - 2194-0517
DOI - 10.1007/s40204-020-00137-0
Subject(s) - extracellular matrix , self healing hydrogels , embryonic stem cell , materials science , biophysics , embryonic heart , biomedical engineering , cardiac fibrosis , viability assay , tissue engineering , scaffold , microbiology and biotechnology , chemistry , cell , fibrosis , biochemistry , pathology , biology , medicine , polymer chemistry , gene
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.