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

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 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.

Effect of Gellan Gum/Tuna Skin Film in Guided Bone Regeneration in Artificial Bone Defect in Rabbit Calvaria

“…GEL can be blended with bio-informative materials that induce regular cell behavior. Koivisoto et al reported that functionalized GEL with gelatin could be the material for biomimicking scaffolds for 3D culture of human cardiomyocytes [17]. Because GEL does not provide attachment for cells, they chose the biofunctionalization of GEL with introduction of gelatin.…”

“…However, GEL, an anionic polysaccharide, can inhibit cell attachment [15]. By blending GEL with bio-informative materials, regular cell behavior can be induced [16,17].…”

“…GEL and gelatin have been studied to build a scaffold for bone regeneration or 3D culture of cardiomyocytes. [14,17]. However, GEL products of complicated modification could be expensive for commercial use; more simple forms of GEL might be more appropriate to meet clinical demand.…”

Bioactive glass ions for in vitro osteogenesis and microvascularization in gellan gum‐collagen hydrogels

“…On the other hand, three‐dimensional (3D) cell culture in hydrogels offers stem cells a microenvironment mimicking the natural. Indeed, according to reports, collagen type I (COL) and polysaccharide gellan gum (GG) are besides biocompatible and bioresorbable hydrophilic natural polymer hydrogels, also suited to bone and vascularization applications (Gantar et al, ; Koivisto et al, ; Manda et al, ; Marelli et al, ; Oliveira, Custodio, Gasperini, Reis, & Mano, ). Also, injectable hydrogel biomaterials facilitate minimally invasive procedures thus avoiding risks of adverse complications (Kondiah et al, ).…”

A Study of the Synergistic Interaction of Konjac Glucomannan/Curdlan Blend Systems under Alkaline Conditions

“…A composite hydrogel with excellent biocompatibility prepared from KGM and carboxymethyl chitosan has been used as a wound dressing for wound healing [5]. In addition, blended polysaccharides have been used in intelligent hydrogels [6,7], aerogels [8], soil improvement [9], food moisture retention [10,11], and biological materials [12,13,14,15]. Studies on the interactions between polysaccharides have important practical application value.…”