ACS Appl Mater Interfaces. 2019 May 23. doi: 10.1021/acsami.8b22343. [Epub ahead of print]

Mechanically Biomimetic Gelatin-Gellan Gum Hydrogels for 3D Culture of Beating Human Cardiomyocytes.

Koivisto JT, Gering C, Karvinen J, Maria Cherian R, Belay B, Hyttinen J, Aalto-Setälä K, Kellomäki M, Parraga J.

Abstract

To promote the transition of cell cultures from 2D to 3D, hydrogels are needed to biomimic the extracellular matrix (ECM). One potential material for this purpose is gellan gum (GG), a biocompatible and mechanically tunable hydrogel. However, GG alone does not provide attachment sites for cells to thrive in 3D. One option for biofunctionalization is the introduction of gelatin, a derivative of the abundant ECM protein collagen. Unfortunately, gelatin lacks crosslinking moieties, making the production of self-standing hydrogels difficult in physiological conditions. Here, we explore the functionalization of GG with gelatin at biologically relevant concentrations using semi-orthogonal, cytocompatible, and facile chemistry based on hydrazone reaction. These hydrogels exhibit mechanical behavior, especially elasticity, which resembles cardiac tissue. The use of optical projection tomography for 3D cell microscopy demonstrates the good cytocompatibility and elongation of human fibroblasts (WI-38). In addition, human induced pluripotent stem cell-derived cardiomyocytes attach to the hydrogels and recover their spontaneous beating at 24 h culture. Beating is studied using in-house built phase contrast video analysis software, and it is comparable with the beating of control cardiomyocytes in regular culture conditions. These hydrogels provide a promising platform to transition cardiac tissue engineering and disease modeling from 2D to 3D.