Engineered hydrogels for mechanobiology

Abstract

Cells’ local mechanical environment can be as important in guiding cellular responses as many well-characterized biochemical cues. Hydrogels that mimic the native extracellular matrix can provide these mechanical cues to encapsulated cells, allowing for the study of their impact on cellular behaviours. Moreover, by harnessing cellular responses to mechanical cues, hydrogels can be used to create tissues in vitro for regenerative medicine applications and for disease modelling. This Primer outlines the importance and challenges of creating hydrogels that mimic the mechanical and biological properties of the native extracellular matrix. The design of hydrogels for mechanobiology studies is discussed, including appropriate choice of cross-linking chemistry and strategies to tailor hydrogel mechanical cues. Techniques for characterizing hydrogels are explained, highlighting methods used to analyze cell behaviour. Example applications for studying fundamental mechanobiological processes and regenerative therapies are provided, along with a discussion of the limitations of hydrogels as mimetics of the native extracellular matrix. The article ends with an outlook for the field, focusing on emerging technologies that will enable new insights into mechanobiology and its role in tissue homeostasis and disease.

Multimodal and Dynamic Cross-Linking of Modular Thiolated Alginate-Based Bioinks

“…However, the presence of reversible covalent disulfide bonds in AlgCP hydrogels makes the network dynamic. 3 Treating the hydrogels with glutathione (GSH) results in reduction of the disulfides, which depending on the extent of intramolecular disulfides, can have a dramatic impact on the hydrogel properties. Without GSH-insensitive thiol-maleimide cross-links, the hydrogel network will be completely disrupted and dissolved upon addition of GSH (5 mM) in less than 30 minutes (Figure 2 a and b).…”

“…However, the complexity, batch-to-batch variability, and varying amount of bioactive factors in these materials can influence experimental reproducibility, which has motivated development of engineered hydrogel systems with more defined compositions. 2,3 Engineered hydrogels can also offer means to tailor cell-hydrogel interactions and possibilities to tune the mechanical and biochemical properties of the materials. [3][4][5] This development is facilitated by hydrogel chemistries that allow for dynamic modulation of hydrogel properties.…”

“…2,3 Engineered hydrogels can also offer means to tailor cell-hydrogel interactions and possibilities to tune the mechanical and biochemical properties of the materials. [3][4][5] This development is facilitated by hydrogel chemistries that allow for dynamic modulation of hydrogel properties. 6,7 Changes in the hydrogel properties can be cell-mediated 8,9 or triggered by various physicochemical or biochemical ques.…”

Modular Enzyme-Responsive Polysaccharide-Based Hydrogels for Biofabrication

“…As our understanding of the role and complexity of ECM in the body has grown, the developed 3D cell culture techniques have aimed to better mimic the physical and biochemical properties of different tissues, rather than just providing physical support. 5 The materials that can provide the closest biological environment to extracellular matrices are decellularized ECMs (dECMs) derived from human or animal tissues. 1 These materials contain most of the components of natural ECMs and can best support cell growth and function.…”

“…Additionally, the use of animal-derived materials raises ethical concerns. 5 The highly hydrated environment of ECM, which facilitates the diffusion of nutrients and soluble factors between cells, can be replicated by a class of materials known as hydrogels. Hydrogels are formed by cross-linking hydrophilic polymer chains together, creating a network that retains water.…”