title: Shear-Thinning Supramolecular Hydrogels with Secondary Autonomous Covalent Crosslinking to Modulate Viscoelastic PropertiesIn Vivo.
abstract: 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, we exploit supramolecular assembly to localize hydrogels at the injection site and introduce subsequent covalent crosslinking to control final material properties. Supramolecular gels were 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 occurred via addition of thiols and Michael-acceptors (i.e., methacrylates, acrylates, vinyl sulfones) on HA and increased hydrogel moduli (E=25.0±4.5kPa) and stability (>3.5 foldin vivoat 28 days). Application of the dual-crosslinking hydrogel to a myocardial infarct model showed 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.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Rodell
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: MacArthur
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States.
authors.forename: Shauna M
authors.initials: SM
authors.lastname: Dorsey
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Wade
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States.
authors.forename: Leo L
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Cardio-Thoracic Surgery, Stanford University School of Medicine, Stanford, California, 94305, United States.
authors.forename: Y Joseph
authors.initials: YJ
authors.lastname: Woo
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
keywords: Michael-addition; hyaluronic acid; hydrogel; injectable; supramolecular assembly