posted on 2020-04-17, 13:43authored byHuey Wen Ooi, Jordy M. M. Kocken, Francis L. C. Morgan, Afonso Malheiro, Bram Zoetebier, Marcel Karperien, Paul A. Wieringa, Pieter J. Dijkstra, Lorenzo Moroni, Matthew B. Baker
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.