Optimization of the methacrylation of carboxymethylcellulose and use for the design of hydrogels and cryogels with controlled structure and properties

Significant research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, impacts fundamental cell processes including spreading, growth, proliferation, migration, differentiation, and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins have become widely-used tools for assessing the role of stiffness, and results from these experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo . However, tissues and ECMs are not linearly elastic materials – they in fact exhibit far more complex mechanical behaviors, including viscoelasticity, or a time-dependent response to loading or deformation, as well as mechanical plasticity and nonlinear elasticity. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and importantly can promote behaviors not observed with elastic hydrogels in both 2D and 3D culture microenvironments. These important findings have provided new insights into cell-matrix interactions and have given context as to how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results indicate new design guidelines for the next generation of biomaterials that better match tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.

Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of tissue engineering scaffolds a topic of great interest in biomedical research. Because of their biocompatibility and similarities to native extracellular matrix, hydrogels have emerged as leading candidates for engineered tissue scaffolds. However, precise control of hydrogel properties, such as porosity, remains a challenge. Traditional techniques for creating bulk porosity in polymers have demonstrated success in hydrogels for tissue engineering; however, often the conditions are incompatible with direct cell encapsulation. Emerging technologies have demonstrated the ability to control porosity and the microarchitectural features in hydrogels, creating engineered tissues with structure and function similar to native tissues. In this review, we explore the various technologies for controlling the porosity and microarchitecture within hydrogels, and demonstrate successful applications of combining these techniques.