Human Induced Pluripotent Stem Cell‐Derived Neural Progenitor Cells Produce Distinct Neural 3D In Vitro Models Depending on Alginate/Gellan Gum/Laminin Hydrogel Blend Properties

Abstract

Stable and predictive neural cell culture models are a necessary premise for many research fields. However, conventional 2D models lack 3D cell‐material/‐cell interactions and hence do not reflect the complexity of the in vivo situation properly. Here two alginate/gellan gum/laminin (ALG/GG/LAM) hydrogel blends are presented for the fabrication of human induced pluripotent stem cell (hiPSC)‐based 3D neural models. For hydrogel embedding, hiPSC‐derived neural progenitor cells (hiNPCs) are used either directly or after 3D neural pre‐differentiation. It is shown that stiffness and stress relaxation of the gel blends, as well as the cell differentiation strategy influence 3D model development. The embedded hiNPCs differentiate into neurons and astrocytes within the gel blends and display spontaneous intracellular calcium signals. Two fit‐for‐purpose models valuable for i) applications requiring a high degree of complexity, but less throughput, such as disease modeling and long‐term exposure studies and ii) higher throughput applications, such as acute exposures or substance screenings are proposed. Due to their wide range of applications, adjustability, and printing capabilities, the ALG/GG/LAM based 3D neural models are of great potential for 3D neural modeling in the future.

Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats

“…Our data showed that it is possible to make RPE and RO co-grafts using alginate as a bio-adhesive. Previous investigations demonstrated that alginate can be used for tissue engineering and other biomedical applications ( Kuo and Ma, 2001 ; Espona-Noguera et al, 2018 ; Hontani et al, 2019 ; Yeo and Kim, 2020 ; Kapr et al, 2021 ). It’s application in wound healing, drug delivery, and tissue engineering is well established due its ability to retain structural similarity to the extracellular matrices in tissues ( Lee and Mooney, 2012 ; Li et al, 2020 ).…”

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

“…Here, only exopolysaccharides (except for bacterial cellulose that was considered in Section 2.2 ) will be reviewed since they are the most commonly used microbial polysaccharides for bioprinting applications [ 26 ]. The usage of these polysaccharides in 3D bioprinting is still gaining ground since the exploitation of microbial-derived polysaccharides-based bioinks has only been recently described in the literature [ 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 ], as summarized in Table 3 .…”

“…Moreover, the presence of carboxylic groups in its structure allows the formation of hydrogels in the presence of mono and divalent ions, such as Na + , K + and Mg 2+ , Ca 2+ , respectively [ 173 ]. Gellan gum hydrogels obtained by ionotropic crosslinking are brittle and mechanically weak, so it is normally necessary to chemically modify [ 157 ] or blend them with other polymers [ 153 , 158 , 159 , 160 , 161 , 162 ] to obtain printable bioinks.…”

Alzheimer’s Disease: Current Perspectives and Advances in Physiological Modeling

“…Scaffold materials are usually selected to fit the paradigms of a particular question of interest. The most used scaffold for 3D neural cell cultures is Matrigel, but others have opted for more specialized tissue-engineering materials, including alginate-gellan gum-laminin blends [ 93 ], microfibrous PLGA [ 94 ], designer self-assembled peptides [ 95 ], and decellularized porcine brain ECM [ 96 ], which has also been tested as an external scaffold for spheroids [ 97 ]. Likewise, an early adopter of 3D culture for AD modeling, Zhang et al [ 98 ], created iPSC-derived neuronal organoids in a 3D matrix made of RADA-16, a self-assembling amphiphilic peptide.…”