No abstract

Hydrogels prepared from supramolecular cross-linking motifs are appealing for use as biomaterials and drug delivery technologies. The inclusion of macromolecules (e.g., protein therapeutics) in these materials is relevant to many of their intended uses. However, the impact of dynamic network cross-linking on macromolecule diffusion must be better understood. Here, hydrogel networks with identical topology but disparate cross-link dynamics are explored. These materials are prepared from cross-linking with host–guest complexes of the cucurbit[7]­uril (CB[7]) macrocycle and two guests of different affinity. Rheology confirms differences in bulk material dynamics arising from differences in cross-link thermodynamics. Fluorescence recovery after photobleaching (FRAP) provides insight into macromolecule diffusion as a function of probe molecular weight and hydrogel network dynamics. Together, both rheology and FRAP enable the estimation of the mean network mesh size, which is then related to the solute hydrodynamic diameters to further understand macromolecule diffusion. Interestingly, the thermodynamics of host–guest cross-linking are correlated with a marked deviation from classical diffusion behavior for higher molecular weight probes, yielding solute aggregation in high-affinity networks. These studies offer insights into fundamental macromolecular transport phenomena as they relate to the association dynamics of supramolecular networks. Translation of these materials from in vitro to in vivo is also assessed by bulk release of an encapsulated macromolecule. Contradictory in vitro to in vivo results with inverse relationships in release between the two hydrogels underscores the caution demanded when translating supramolecular biomaterials into application.

Strain-stiffening is observed and characterized in flexible PEG hydrogel networks crosslinked via dynamic-covalent boronate ester bonds, revealing an uncommon synthetic mimic of a mechanoresponse found in natural biopolymer networks.

Methods to predict the equilibrium solubility of nonelectrolyte solids are indispensable for early-stage process development, design, and feasibility studies. Conventional analytic methods typically require reference data to regress parameters, which may not be available or limited for novel systems. Molecular simulation is a promising alternative, but is computationally intensive. Here, we demonstrate the ability to use a small number of molecular simulation free energy calculations to generate reference data to regress model parameters for the analytical MOSCED (modified separation of cohesive energy density) model. The result is an efficient analytical method to predict the equilibrium solubility of nonelectrolyte solids. The method is demonstrated for the wastewater contaminants monuron, diuron, atrazine and atenolol. Predictions for monuron, diuron and atrazine are in reasonable agreement with MOSCED parameters regressed using experimental solubility data. Predictions for atenolol are inferior, suggesting a potential limitation in the adopted molecular models, or the solvents selected to generate the necessary reference data.