Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three‐Dimensional Hydrogels

Abstract

Morphogens are biological molecules that alter cellular identity and behavior across both space and time. During embryonic development, morphogen spatial localization can be confined to small volumes in a single tissue or permeate throughout an entire organism, and the temporal effects of morphogens can range from fractions of a second to several days. In most cases, morphogens are presented as a gradient to adjacent cells within tissues to pattern cell fate. As such, to appropriately model development and build representative multicellular architectures in vitro, it is vital to recapitulate these gradients during stem cell differentiation. However, the ability to control morphogen presentation within in vitro systems remains challenging. Here, we describe an innovative platform using channels patterned within thick, three‐dimensional hydrogels that deliver multiple morphogens to embedded cells, thereby demonstrating exquisite control over both spatial and temporal variations in morphogen presentation. This generalizable approach should have broad utility for researchers interested in patterning in vitro tissue structures. © 2019 by John Wiley & Sons, Inc.

Recent Advancements in Engineering Strategies for Manipulating Neural Stem Cell Behavior

“…Although morphogen presentation using microfluidic devices has yielded success for patterning in embryonic cultures, the size of such culture platforms limits the ability to pattern larger and more complex neural tissues. These problems may be overcome using larger hydrogel systems that facilitate morphogen gradient generation across millimeter distances [58,59]. Further, the regulation of neural cell behavior within biomimetic hydrogels has been mainly focused on binary fate decisions (e.g., NSC self-renewal versus differentiation, differentiation to neurons versus astrocytes) rather than more complex events such as differentiation and organization of iPSC-derived neuron subclasses into complex, functional circuits.…”

Recent Developments in 3D Bio-Printing and Its Biomedical Applications

“…Both natural and artificial polymers are used in bio-inks because of the substances that are appropriate for them. Bio-inks are being used to create 3D-printed constructions using a broad range of materials (ceramics, hydrogels, elastomers, and polymers) [ 29 ]. The highlights and drawbacks of these materials for 3D bio-printing are discussed in this section.…”

Circulating MicroRNAs and Blood-Brain-Barrier Function in Breast Cancer Metastasis

“…Moreover, a defined ECM is important to provide physical stabilization and provides molecules essential to develop BBB characteristics. Platforms using channels structured in thick three-dimensional hydrogels could provide a useful tool for multicellular approaches in vitro by mimicking tissue structures that play a role in differentiating EPCs [ 144 ]. On one hand, defined ECM can be achieved by chemically applied substrates or by cultivating brain capillary-like ECs with other types of cells building the NVU.…”