Multivalency Enables Dynamic Supramolecular Host–Guest Hydrogel Formation

Abstract

Supramolecular and dynamic biomaterials hold promise to recapitulate the time-dependent properties and stimuli-responsiveness of the native extracellular matrix (ECM). Host−guest chemistry is one of the most widely studied supramolecular bonds, yet the binding characteristics of host−guest complexes (β-CD/adamantane) in relevant biomaterials have mostly focused on singular host−guest interactions or nondiscrete multivalent pendent polymers. The stepwise synergistic effect of multivalent host−guest interactions for the formation of dynamic biomaterials remains relatively unreported. In this work, we study how a series of multivalent adamantane (guest) cross-linkers affect the overall binding affinity and ability to form supramolecular networks with alginate-CD (Alg-CD). These binding constants of the multivalent cross-linkers were determined via NMR titrations and showed increases in binding constants occurring with multivalent constructs. The higher multivalent cross-linkers enabled hydrogel formation; furthermore, an increase in binding and gelation was observed with the inclusion of a phenyl spacer to the cross-linker. A preliminary screen shows that only cross-linking Alg-CD with an 8-arm-multivalent guest results in robust gel formation. These cytocompatible hydrogels highlight the importance of multivalent design for dynamically cross-linked hydrogels. These materials hold promise for development toward cell-and small molecule-delivery platforms and allow discrete and fine-tuning of network properties.

The rheology of direct and suspended extrusion bioprinting

“…102 This allows for a range of mechanical properties to be achieved by using different or multiple interactions in designing a bioink. 105 Several classes of supramolecular chemistry have been used in bioink formulations including guest-host complexes, 106 supramolecular polymers, 104 supramolecular polymer networks, and self-assembled architectures. 107 …”

From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances

“…This provides greater predictability and reproducibility of hydrogel properties. The reversibility of the host–guest interaction gives the hydrogels self-healing and shear-thinning properties [ 11 , 36 , 58 , 59 , 60 ].…”

“…They have a hydrophilic external and relatively hydrophobic inner cavity. The small-cavity, α-CD, incorporates mainly linear guest molecules, while β-CD interacts with adamantane, azobenzene, ferrocene, cholesterol, and PEG ( Figure 5 ) [ 13 , 36 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. The CD units can be incorporated into cyclodextrin-polymers (e.g., polyrotaxanes), as well as being grafted to other polymer chains, e.g., alginate, HA, PEG, and PAA.…”

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

“…Recently, the development of advanced synthetic matrices (reviewed in ref. [ 68 ] ), such as functionalized host–guest supramolecular hydrogels, [ 69 ] has been recognized as a versatile platform for investigating complex biological processes to account for the inherent dynamicity of such systems.…”