Synthetic hydrogels formed from poly(ethylene glycol) (PEG) are widely used to study how cells interact with their extracellular matrix. These in vivo-like 3D environments provide a basis for tissue engineering and cell therapies but also for research into fundamental biological questions and disease modeling. The physical properties of PEG hydrogels can be modulated to provide mechanical cues to encapsulated cells; however, the impact of changing hydrogel stiffness on the diffusivity of solutes to and from encapsulated cells has received only limited attention. This is particularly true in selectively cross-linked "tetra-PEG" hydrogels, whose design limits network inhomogeneities. Here, we used a combination of theoretical calculations, predictive modeling, and experimental measurements of hydrogel swelling, rheological behavior, and diffusion kinetics to characterize tetra-PEG hydrogels' permissiveness to the diffusion of molecules of biologically relevant size as we changed polymer concentration, and thus hydrogel mechanical strength. Our models predict that hydrogel mesh size has little effect on the diffusivity of model molecules and instead predicts that diffusion rates are more highly dependent on solute size. Indeed, our model predicts that changes in hydrogel mesh size only begin to have a non-negligible impact on the concentration of a solute that diffuses out of hydrogels for the smallest mesh sizes and largest diffusing solutes. Experimental measurements characterizing the diffusion of fluorescein isothiocyanate (FITC)-labeled dextran molecules of known size aligned well with modeling predictions and suggest that doubling the polymer concentration from 2.5% (w/v) to 5% produces stiffer gels with faster gelling kinetics without affecting the diffusivity of solutes of biologically relevant size but that 10% hydrogels can slow their diffusion. Our findings provide confidence that the stiffness of tetra-PEG hydrogels can be modulated over a physiological range without significantly impacting the transport rates of solutes to and from encapsulated cells.

Self‐assembly of supramolecular hydrogels is driven by dynamic, non‐covalent interactions between molecules. Considerable research effort has been exerted to fabricate and optimise supramolecular hydrogels that display shear‐thinning, self‐healing, and reversibility, in order to develop materials for biomedical applications. This review provides a detailed overview of the chemistry behind the dynamic physicochemical interactions that sustain hydrogel formation (hydrogen bonding, hydrophobic interactions, ionic interactions, metal‐ligand coordination, and host‐guest interactions). Novel design strategies and methodologies to create supramolecular hydrogels are highlighted, which offer promise for a wide range of applications, specifically drug delivery, wound healing, tissue engineering and 3D bioprinting. To conclude, future prospects are briefly discussed, and consideration given to the steps required to ultimately bring these biomaterials into clinical settings.

Supramolecular hydrogels are generated when gelator molecules (or macromolecules) spontaneously self‐assemble to form a 3D solid‐like network via dynamic intermolecular non‐covalent bonds, such as hydrogen bonding, π‐π bonding, hydrophobic interactions, and van der Waals interactions. Here, the interactions that underlie the formation of supramolecular hydrogels are presented, before exemplifying their versatility by highlighting a selection of recent state‐of‐the‐art developments and their associated biomedical applications. The applications selected include drug delivery, tissue engineering, wound healing and 3D bioprinting. More information can be found in the Review by Xian Jun Loh, Cécile A. Dreiss, Tung‐Chun Lee et al.