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

IF 4.4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Progress in Biomaterials Pub Date : 2020-09-01 Epub Date: 2020-09-25 DOI:10.1007/s40204-020-00137-0
Matthew Alonzo, Shweta Anil Kumar, Shane Allen, Monica Delgado, Fabian Alvarez-Primo, Laura Suggs, Binata Joddar
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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.

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具有模拟胚胎基质弹性的水凝胶支架可促进心脏细胞网络的形成。
水凝胶是一类生物材料,可广泛应用于生物医学领域,包括作为细胞培养的三维(3D)支架,模拟原生组织的细胞外基质(ECM)。为了了解 ECM 在调节心脏细胞功能中的作用,我们使用藻酸盐制造交联凝胶,其硬度值分别与胚胎(2.66 ± 0.84 kPa)、生理性(8.98 ± 1.29 kPa)和纤维化(18.27 ± 3.17 kPa)心脏组织相似。平均孔径和水凝胶膨胀随着基质硬度的增加而减小。在柔软的胚胎凝胶中培养的心肌细胞表现出更强的细胞铺展、伸长和网络形成能力,而凝胶硬度的逐渐增加会削弱这些行为。细胞活力随着水凝胶硬度的增加而降低。此外,与胚胎凝胶中的细胞相比,纤维化凝胶中细胞的特征性心脏应激生物标志物肌钙蛋白-I的蛋白表达增强,而心脏间隙连接蛋白Connexin-43的蛋白表达降低。这项研究的结果证明了三维基质硬度对心脏组织形成的作用,以及它在心肌纤维化等基于基质重塑的复杂病症发展过程中的意义。
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来源期刊
Progress in Biomaterials
Progress in Biomaterials MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
9.60
自引率
4.10%
发文量
35
期刊介绍: Progress in Biomaterials is a multidisciplinary, English-language publication of original contributions and reviews concerning studies of the preparation, performance and evaluation of biomaterials; the chemical, physical, biological and mechanical behavior of materials both in vitro and in vivo in areas such as tissue engineering and regenerative medicine, drug delivery and implants where biomaterials play a significant role. Including all areas of: design; preparation; performance and evaluation of nano- and biomaterials in tissue engineering; drug delivery systems; regenerative medicine; implantable medical devices; interaction of cells/stem cells on biomaterials and related applications.
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