Multivalency Enables Dynamic Supramolecular Host-Guest Hydrogel Formation

Huey 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

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 (beta-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 titration 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.

Original languageEnglish
Pages (from-to)2208-2217
Number of pages10
JournalBiomacromolecules
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • DOUBLE-NETWORK HYDROGELS
  • BETA-CYCLODEXTRIN
  • ALGINATE
  • ADAMANTANE
  • CHEMISTRY
  • COMPLEXATION
  • ASSOCIATION
  • DESIGN

Cite this