Shear-Thinning Supramolecular Hydrogels with Secondary Autonomous Covalent Crosslinking to Modulate Viscoelastic Properties In Vivo

Clinical percutaneous delivery of synthetically engineered hydrogels remains limited due to challenges posed by crosslinking kinetics—too fast leads to delivery failure, too slow limits material retention. To overcome this challenge, supramolecular assembly is exploited to localize hydrogels at the...

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Bibliographic Details
Published in:Advanced functional materials 2015-01, Vol.25 (4), p.636-644
Main Authors: Rodell, Christopher B., MacArthur Jr, John W., Dorsey, Shauna M., Wade, Ryan J., Wang, Leo L., Woo, Y. Joseph, Burdick, Jason A.
Format: Article
Language:English
Subjects:
Biomedical materials
Covalence
Crosslinking
Hyaluronic acid
Hydrogels
Hydroxyapatite
In vivo tests
injectables
Michael-addition
supramolecular assembly
Surgical implants
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Summary:Clinical percutaneous delivery of synthetically engineered hydrogels remains limited due to challenges posed by crosslinking kinetics—too fast leads to delivery failure, too slow limits material retention. To overcome this challenge, supramolecular assembly is exploited to localize hydrogels at the injection site and introduce subsequent covalent crosslinking to control final material properties. Supramolecular gels are designed through the separate pendant modifications of hyaluronic acid (HA) by the guest–host pair cyclodextrin and adamantane, enabling shear‐thinning injection and high target site retention (>98%). Secondary covalent crosslinking occurs via addition of thiols and Michael‐acceptors (i.e., methacrylates, acrylates, vinyl sulfones) on HA and increases hydrogel moduli (E = 25.0 ± 4.5 kPa) and stability (>3.5 fold in vivo at 28 d). Application of the dual‐crosslinking hydrogel to a myocardial infarct model shows improved outcomes relative to untreated and supramolecular hydrogel alone controls, demonstrating its potential in a range of applications where the precise delivery of hydrogels with tunable properties is desired. Injectable hyaluronic acid hydrogels with high target site retention, tunable properties, and potential for percutaneous delivery are developed through a tandem crosslinking approach. Supramolecular crosslinking provides initial hydrogel formation and shear‐thinning delivery, while secondary covalent crosslinking stabilizes the hydrogel in situ. Material properties and treatment of myocardial infarct are examined.
ISSN:1616-301X
1616-3028
DOI:10.1002/adfm.201403550