title: An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart.
abstract: Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the limited access to donor hearts. An example of a treatment to recover the function of the heart consists of the local delivery of drugs and bioactives from a hydrogel. In this paper a method is introduced to formulate and inject a drug-loaded hydrogel non-invasively and side-specific into the pig heart using a long, flexible catheter. The use of 3-D electromechanical mapping and injection via a catheter allows side-specific treatment of the myocardium. To provide a hydrogel compatible with this catheter, a supramolecular hydrogel is used because of the convenient switching from a gel to a solution state using environmental triggers. At basic pH this ureido-pyrimidinone modified poly(ethylene glycol) acts as a Newtonian fluid which can be easily injected, but at physiological pH the solution rapidly switches into a gel. These mild switching conditions allow for the incorporation of bioactive drugs and bioactive species, such as growth factors and exosomes as we present here in both in vitro and in vivo experiments. The in vitro experiments give an on forehand indication of the gel stability and drug release, which allows for tuning of the gel and release properties before the subsequent application in vivo. This combination allows for the optimal tuning of the gel to the used bioactive compounds and species, and the injection system.
authors.affiliation: Institute for Complex Molecular Systems, Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology.
authors.forename: A C H
authors.initials: AC
authors.lastname: Pape
authors.affiliation: Institute for Complex Molecular Systems, Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology.
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Bakker
authors.affiliation: Department of Cardiology, Division Heart and Lungs, Interuniversity Cardiology Institute of the Netherlands (ICIN), University Medical Center Utrecht.
authors.forename: Cheyenne C S
authors.initials: CC
authors.lastname: Tseng
authors.affiliation: Institute for Complex Molecular Systems, Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology.
authors.forename: Maartje M C
authors.initials: MM
authors.lastname: Bastings
authors.affiliation: Department of Cardiology, Division Heart and Lungs, Interuniversity Cardiology Institute of the Netherlands (ICIN), University Medical Center Utrecht.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koudstaal
authors.affiliation: Department of Cardiology, Division Heart and Lungs, Interuniversity Cardiology Institute of the Netherlands (ICIN), University Medical Center Utrecht.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Agostoni
authors.affiliation: Department of Cardiology, Division Heart and Lungs, Interuniversity Cardiology Institute of the Netherlands (ICIN), University Medical Center Utrecht.
authors.forename: Steven A J
authors.initials: SA
authors.lastname: Chamuleau
authors.affiliation: Institute for Complex Molecular Systems, Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology; P.Y.W.Dankers@tue.nl.
authors.forename: Patricia Y W
authors.initials: PY
authors.lastname: Dankers
mesh_terms: D000818:Animals; D006328:Cardiac Catheterization / Q000379:methods*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D011744:Pyrimidinones / Q000737:chemistry; D013552:Swine
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D011744:Pyrimidinones