Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation
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ORIGINAL RESEARCH
Hydrogel scaffolds with elasticity‑mimicking embryonic substrates promote cardiac cellular network formation Matthew Alonzo1,2 · Shweta Anil Kumar1,2 · Shane Allen4 · Monica Delgado1,2 · Fabian Alvarez‑Primo1,2 · Laura Suggs4 · Binata Joddar1,2,3 Received: 22 June 2020 / Accepted: 17 September 2020 © Islamic Azad University 2020
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. Keywords Alginate · Cardiomyocytes · Elastic modulus · Cell viability · Scaffold stiffness
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40204-020-00137-0) contains supplementary material, which is available to authorized users. * Binata Joddar [email protected] 1
Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), El Paso, USA
2
Department of Metallurgical, Materials and Biomedical Engineering, M201 Engineering, The University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, USA
3
Border Biomedical Research Center, The University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, USA
4
Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA
Tissue stiffness is a dynamic biomechanical property that influences organismal development and physiology (Chen and Liu 2016; Stowers et al. 2015). As the extracellular matrix (ECM) undergoes remodeling during various biological processes, the mechanical properties of the environment in which living cells are embedded change accordingly. It is well established that variances in substrate stiffness can affect cellular migration, alignment, proliferation, morphology, and differentiation (Lee and Mooney 2001; Yang
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