Polymeric materials based on reversible non-covalent associations possess diverse mechanical behaviour, responsiveness to external stimuli and self-healing properties. Unlike covalently-bonded polymeric materials, whose properties are conventionally engineered through the polymer structure alone, the mechanical performance of a supramolecular material can be designed via two motifs: the polymer architecture (e.g., polymer molecular weight or structure) and the physical crosslinks (e.g., thermodynamics or kinetics of binding) between polymers. Here, we demonstrate the preparation of aqueous-based supramolecular polymeric materials utilising cucurbit[8]uril (CB[8]) crosslinking of multivalent polymers of varying molecular weights. By exploiting three kinetically distinct supramolecular motifs, we show that it is possible to relate the contributions of polymer architecture and dynamic crosslinking to the ultimate mechanical properties of the materials. These studies improve our understanding of the challenging relationships between design of supramolecular polymeric materials and their complex viscoelastic behaviour as well as relaxation dynamics.

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.

Background: Hyaluronic acid (HA) is the major component of the extracellular matrix in the central nervous system and the only supramolecular glycosaminoglycan. Much focus has been given to using this high molecular weight polysaccharide for tissue engineering applications. In the majority of cases, HA is covalently functionalized with moieties that can facilitate network formation through physical selfassembly, or photo-catalyzed covalent crosslinking as the polysaccharide does not gel on its own. However, these covalent crosslinks are not the driving force of HA self-assembly in biological tissues. Methods: Oscillatory rheology and dynamic light scattering were used to study albumin/HA structures. Dynamic light scattering and transmission electron microscopy were used to study albumin/chondroitin sulfate (CS) structures. UV-vis spectroscopy was used to study mass transfer of a hydrophilic small molecule into the albumin/HA/CS materials. Results: In this work we examine the intermolecular interactions of two major glycans found in the human brain, HA and the lower molecular weight CS , with the protein albumin. We report physiochemical properties of the resulting supramolecular micro- and nanomaterials. Albumin/HA mixtures formed supramolecular gels, and albumin/CS mixtures formed micro- and nanoparticles. We also summarize the concentrations of HA and CS found in various mammalian brains. Conclusions: Simple preparation and combination of commercially available charged biomacromolecules under short time-scales can result in interesting self-assembled materials with structures at the micron and nanometer length-scales. Such materials may have utility in serving as cost-effective and simple models of nervous system electrostatic interactions and as in vitro drug release and mass transfer quantification tools.