Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation
Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation
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DOI：
10.1007/s40204-020-00137-0
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发表时间：
2020-09-25
影响因子：
4.9
通讯作者：
Joddar, Binata
中科院分区：
文献类型：
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作者：
Alonzo, Matthew;Kumar, Shweta Anil;Joddar, Binata
水凝胶是一类广泛用于生物医学应用的生物材料，包括作为细胞培养的三维（3D）支架，模拟天然组织的细胞外基质（ECM）。为了了解ECM在心脏细胞功能调节中的作用，用海藻酸盐制备了硬度值类似于胚胎（2.66 +/- 0.84 kPa）、生理（8.98 +/- 1.29 kPa）和纤维化（18.27 +/- 3.17 kPa）心脏组织的交联凝胶。平均孔径和水凝胶膨胀随基质刚度的增加而减小。在软胚胎凝胶中培养的心肌细胞表现出增强的细胞扩散、伸长和网络形成，而凝胶硬度的逐渐增加会减弱这些行为。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，纤维化凝胶中的细胞表现出心脏应激生物标志物肌钙蛋白- 1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3D基质刚度对心脏组织形成的作用，以及它在复杂基质重塑疾病（如心肌纤维化）发展中的意义。
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.