Modeling development using hydrogels

Abstract

The development of multicellular complex organisms relies on coordinated signaling from the microenvironment, including both biochemical and mechanical interactions. To better understand developmental biology, increasingly sophisticated in vitro systems are needed to mimic these complex extracellular features. In this Primer, we explore how engineered hydrogels can serve as in vitro culture platforms to present such signals in a controlled manner and include examples of how they have been used to advance our understanding of developmental biology.

Keywords: In vitro culture; Extracellular matrix; Hydrogels; Mechanobiology.

Fig. 1.

Engineering hydrogels to present extracellular signals to cells. Hydrogels consist of polymer networks in which polymer composition (natural, synthetic or hybrid polymers), polymer crosslinking (covalent or physical) and network degradation (user-mediated and cell-mediated) can be tuned. In addition, biological signals may be introduced as ligands to promote cell adhesion or as soluble factors. Cells interface with hydrogels either through seeding atop (2D) or being encapsulated within (3D).

Fig. 2.

Increasing complexity of extracellular environments through hydrogels. Hydrogels can be engineered to recapitulate aspects of extracellular environments. For example, they can be designed to display cell-cell (A) and cell-ECM (B) moieties. In addition, hydrogels may present various 2D uniform (left), gradient (middle) or patterned (right) molecular cues to guide cellular behaviors (C) or pseudo 3D topologies such as microgrooves (left), fibrous structures (middle) or through folding or buckling of 2D substrates (right panel) (D).

Fig. 3.

Examples of higher-order hydrogel fabrication for increasingly complex architectures. (A) Intestinal organoids in Matrigel typically form buds in a variable manner (left panel). However, hydrogels can be used to support organoid culture and guide morphogenesis in a fully defined and reproducible manner whereby organoids consistently form crypt-like buds along photo-softened areas (right panel). Based on studies from Gjorevski et al. (2022). (B) Hydrogels can also be used within microfluidics to direct spatial embryonic development into 3D structures within hydrogel compartments that modulate environmental signals. Adapted with permission from Bonner et al. (2022), which was re-drawn from Zheng et al. (2019).

Fig. 4.

Modeling morphogenesis using hydrogels. (A) DNA-programmed assembly of cells allows the precise engineering of hydrogel folding to study this crucial developmental morphogenetic process. Based on studies from Hughes et al. (2018). (B) The temporal addition of other extracellular cues and morphogen patterns can also promote patterning. Based on studies from Karzbrun et al. (2021).