Selectively Cross-Linked Tetra-PEG Hydrogels Provide Control over Mechanical Strength with Minimal Impact on Diffusivity

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 research into fundamental biological questions disease modeling. The physical properties of PEG can be modulated mechanical cues encapsulated cells; however, the impact changing hydrogel stiffness on diffusivity solutes has received only limited attention. This is particularly true selectively cross-linked “tetra-PEG” hydrogels, whose design limits network inhomogeneities. Here, we combination theoretical calculations, predictive modeling, experimental measurements swelling, rheological behavior, diffusion kinetics characterize tetra-PEG hydrogels’ permissiveness molecules biologically relevant size as changed polymer concentration, thus strength. Our models predict that mesh little effect model instead predicts rates more highly dependent solute size. Indeed, our changes begin have non-negligible concentration diffuses out smallest sizes largest diffusing solutes. Experimental characterizing fluorescein isothiocyanate (FITC)-labeled dextran known aligned well modeling predictions suggest doubling 2.5% (w/v) 5% produces stiffer gels faster gelling without affecting 10% slow diffusion. findings confidence over physiological range significantly impacting transport cells.