Rational Design of Network Properties in Guest–Host Assembled and Shear-Thinning Hyaluronic Acid Hydrogels

Abstract

Shear-thinning hydrogels afford direct injection or catheter delivery to tissues without potential premature gel formation and delivery failure or the use of triggers such as chemical initiators or heat. However, many shear-thinning hydrogels require long reassembly times or exhibit rapid erosion. We developed a shear-thinning hyaluronic acid (HA) hydrogel based on the guest-host interactions of adamantane modified HA (guest macromer, Ad-HA) and β-cyclodextrin modified HA (host macromer, CD-HA). The ability of the guest and host molecules to interact with their counterpart following conjugation to HA was confirmed by 1H-NMR spectroscopy and was similar to that of the native complex. Mixing of Ad-HA and CD-HA resulted in rapid formation of a hydrogel composed of guest-host bonds. The hydrogel physical properties including mechanics and flow characteristics were dependent on crosslink density and network structure, which were controlled through macromer concentration, the extent of guest macromer modification, and the molar ratio of guest and host functional groups. The guest-host assembly mechanism permitted both shear-thinning behavior for ease of injection and near-instantaneous reassembly for material retention at the target sight. The hydrogel erosion and release of a model biomolecule were also dependent on design parameters and were sustained for over 60 days. These hydrogels show potential as a minimally-invasive injectable hydrogel for biomedical applications.

Supramolecular hydrogels cross-linked by preassembled host–guest PEG cross-linkers resist excessive, ultrafast, and non-resting cyclic compression

“…However, researchers have paid little attention to the energy dissipation capacity of the supramolecular hydrogels crosslinked by the βCD-ADA complexes, mainly because of the mechanical weakness of such hydrogels. Most of the such weak host-guest hydrogels were formed by mixing βCD-modified polymers with ADA-modified polymers and verified with the "tube-inversion" test 10,31,32 . Recently, Harada et al fabricated highly elastic polyacrylamide hydrogels cross-linked by host-guest cross-linkers that are preassembled from βCD monomers and ADA monomers 33,34 .…”

“…To overcome these limitations of conventional chemical hydrogels, researchers have capitalized on a wide array of physical interactions to develop physical hydrogels with unique properties, including self-healing and shearthinning [5][6][7] . However, conventional physical hydrogels are usually too weak to be implanted in load-bearing sites of clinical interest, such as the knee joint 5,[8][9][10] . Thus, the development of strategies to improve the mechanical properties of hydrogel scaffolds, such as mechanical resilience and fatigue resistance, has become crucial to the research field of hydrogels.…”

Introduction

“…Poly (organophosphazene) structures based on noncovalent inclusion complexation were also used to prepare supramolecular gels that respond to stimuli [19]. Additionally, a minimally invasive injectable shear-thinning HA hydrogel [20] was developed through host-guest interactions between Ada-modified HA (guest macromer) and β-CD-modified HA (host macromer). The host-guest assembly mechanism made the injection easy due to the shear-thinning behavior and facilitated the rapid reassembly needed for material retention at the target.…”

Supramolecular Polymeric Materials Containing Cyclodextrins

“…As examples for method 1), when polymers containing guest residues are mixed with polymers carrying CDs, they form gels through cross-linking by hostguest interaction. [37][38][39] As an example for method 2), when acrylamide modified with Ad residue (Ad-AAm) was mixed with acrylamide modified with βCD (βCD-AAm) in water, Ad-AAm was solubilized in water, indicating complex formation with βCD-AAm. The resultant pair of host-guest monomers was terpolymerized with water soluble vinyl monomer in forming a hydrogel.…”