Mechanically Biomimetic Gelatin-Gellan Gum Hydrogels for 3D Culture of Beating Human Cardiomyocytes.
Janne T KoivistoChristine GeringJennika KarvinenReeja Maria CherianBirhanu BelayJari A K HyttinenKatriina Aalto-SetäläMinna KellomäkiJenny ParragaPublished in: ACS applied materials & interfaces (2019)
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 cross-linking moieties, making the production of self-standing hydrogels difficult under physiological conditions. Here, we explore the functionalization of GG with gelatin at biologically relevant concentrations using semiorthogonal, cytocompatible, and facile chemistry based on hydrazone reaction. These hydrogels exhibit mechanical behavior, especially elasticity, which resembles the cardiac tissue. The use of optical projection tomography for 3D cell microscopy demonstrates 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 in 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 under regular culture conditions. These hydrogels provide a promising platform to transition cardiac tissue engineering and disease modeling from 2D to 3D.
Keyphrases
- tissue engineering
- extracellular matrix
- endothelial cells
- hyaluronic acid
- high glucose
- induced pluripotent stem cells
- single cell
- magnetic resonance
- drug delivery
- pluripotent stem cells
- induced apoptosis
- high throughput
- computed tomography
- drug release
- left ventricular
- magnetic resonance imaging
- stem cells
- high speed
- climate change
- single molecule
- endoplasmic reticulum stress
- atrial fibrillation
- quantum dots
- signaling pathway
- diabetic rats
- contrast enhanced
- bone regeneration
- optical coherence tomography